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Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
Authors: Heredia, David | Bolaño-Guerra, Laura | Valencia-Velarde, Angel | Santoyo, Edgar Varela | Lara-Mejía, Luis | Cárdenas-Fernández, Daniela | Orozco, Mario | Cruz-Rico, Graciela | Arrieta, Oscar
Article Type: Research Article
Abstract: BACKGROUND: Liquid biopsy (LB) is used to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and has been demonstrated to have prognostic and predictive value. OBJECTIVE: To associate the rates of EGFR and T790M mutations detected by LB during disease progression after first- or second-generation EGFR-TKIs with clinical characteristics and survival outcomes. METHODS: From January 2018 to December 2021, 295 patients with advanced EGFR mutant (EGFRm) NSCLC treated with first- or second-generation EGFR-TKIs were retrospectively analyzed. LB was collected at the time of progression. The frequency of …EGFR T790M mutations, overall survival (OS), and the clinical characteristics associated with LB positivity were determined. RESULTS: The prevalence of EGFR T790M mutation detected using LB was 44%. In patients with negative vs. positive LB, the median OS was 45.0 months vs. 25.0 months (p = 0.0001), respectively. Patients with a T790M mutation receiving osimertinib had a median OS of 44 months (95% CI [33.05–54.99]). Clinical characteristics associated with positive LB at progression extra-thoracic involvement, > 3 metastatic sites, and bone metastases. CONCLUSIONS: Our findings showed that LB positivity was associated with worse survival outcomes and specific clinical characteristics. This study also confirmed the feasibility and detection rate of T790M mutation in a Latin American population. Show more
Keywords: EGFRm NSCLC, liquid biopsy, T790M mutation, osimertinib, ctDNA
DOI: 10.3233/CBM-230124
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Karamti, Hanen | Alharthi, Raed | Umer, Muhammad | Shaiba, Hadil | Ishaq, Abid | Abuzinadah, Nihal | Alsubai, Shtwai | Ashraf, Imran
Article Type: Research Article
Abstract: Breast cancer is a major cause of female deaths, especially in underdeveloped countries. It can be treated if diagnosed early and chances of survival are high if treated appropriately and timely. For timely and accurate automated diagnosis, machine learning approaches tend to show better results than traditional methods, however, accuracy lacks the desired level. This study proposes the use of an ensemble model to provide accurate detection of breast cancer. The proposed model uses the random forest and support vector classifier along with automatic feature extraction using an optimized convolutional neural network (CNN). Extensive experiments are performed using the original, …as well as, CNN-based features to analyze the performance of the deployed models. Experimental results involving the use of the Wisconsin dataset reveal that CNN-based features provide better results than the original features. It is observed that the proposed model achieves an accuracy of 99.99% for breast cancer detection. Performance comparison with existing state-of-the-art models is also carried out showing the superior performance of the proposed model. Show more
Keywords: Breast cancer detection, image processing, healthcare, machine learning, ensemble learning, deep convoluted features
DOI: 10.3233/CBM-230294
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2023
Authors: Yao, Ningning | Hou, Qing | Liang, Yu | Cao, Xin | Sun, Bochen | Wei, Lijuan | Sun, Ruifang | Cao, Jianzhong
Article Type: Research Article
Abstract: BACKGROUND: Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. OBJECTIVE: This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). METHODS: We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups’ overall survival (OS) and progression-free survival (PFS). RESULTS: Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in …the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. CONCLUSION: AST might represent a significant prognostic marker for ENKTL patients. Show more
Keywords: Serum aspartate aminotransferase, extranodal natural killer/T cell lymphoma, nasal type, survival, prognosis
DOI: 10.3233/CBM-230068
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Vo, Duc | Liu, Yan | Sood, Anil K. | Rezvani, Katy | Jazaeri, Amir A. | Liu, Jinsong
Article Type: Research Article
Abstract: High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of …EGFR and HLA-G, a second separated cohort of 248 patients is used. Positive EGFR expression again shows worse OS, while HLA-G expression has worse prognostic trend. CD70 has a worse OS trend. C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials. Show more
Keywords: EGFR, HLA-G, CD70, c-MET, NY-ESO1, survival
DOI: 10.3233/CBM-230200
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2023
Authors: Zhou, Sixu | Wang, Baogui | Wei, Yingying | Dai, Peiru | Chen, Yan | Xiao, Yingyi | Xia, Hongmei | Chen, Chunlin | Yin, Weihua
Article Type: Research Article
Abstract: BACKGROUND: Docetaxel is a yew compound antitumor agent with accurate antitumor efficacy, but its application is limited due to the high and serious adverse effects, and finding effective combination therapy options is a viable strategy. Immune checkpoint inhibitors have become hotspots in enhancing anti-tumor immunity by blocking immune checkpoint signaling pathways, but their response rate to monotherapy use is not high and the efficacy is minimal. OBJECTIVE: To explore the anti-tumor effects and mechanisms of the combination of PD-1 inhibitors and Docetaxel through in vivo experiments and develop a feasible combination treatment for the therapy of …prostate cancer. METHODS: Tumor-bearing mice were subcutaneously injected with 0.1 ml RM-1 cells. Treatment were taken when the tumor growed up to 3 mm, after which the tumor and spleen were removed to test the antitumor effect with Flow cytometric (FACS) analysis, Immunohistochemistry, Western Blot. RESULTS: In this experiment, we found that PD-1 inhibitors combined with Docetaxel had a synergistic effect on mouse prostate cancer, inhibited the growth of prostate cancer, improved survival and reduced adverse reactions, increased spleen and tumor infiltrative CD4 + and CD8 + T cells, especially in group combination with low-dose Docetaxel, and were related to the PI3K/AKT/NFKB-P65/PD-L1 signaling pathway. CONCLUSION: Our study confirms that PD-1 inhibitors in combination with Docetaxel are a viable combination strategy and provide a safe and effective combination option for the clinical treatment of prostate cancer. Show more
Keywords: Prostate cancer, docetaxel, PD-1 inhibitor, camrelizumab, immune checkpoints
DOI: 10.3233/CBM-230090
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Yan, Shunkang | Zhang, Jiandong | Li, Lianghe | Chen, Gang | Chen, Zhongsheng | Zhan, Wei
Article Type: Research Article
Abstract: BACKGROUND: Colorectal cancer (CRC) is a common form of cancer, with rectal cancer accounting for approximately one-third of all cases. Among rectal cancers, 95% are classified as rectal adenocarcinoma (READ). Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a significant role in the development and progression of various cancers. In our study, we aimed to identify differentially expressed lncRNAs potentially associated with m6A and establish a risk assessment model to predict clinical outcomes for READ patients. METHODS: The READ dataset from the TCGA database was utilized in this study to synergistically and logically integrate m6A …and lncRNA, while employing bioinformatics technology for the identification of suitable biomarkers. A risk prediction model comprising m6A-associated lncRNAs was constructed to investigate the prognostic, diagnostic, and biological functional relevance of these m6A-related lncRNAs. RESULTS: Our research builds a composed of three related to m6A lncRNA rectal gland cancer prognosis model, and the model has been proved in the multi-dimensional can serve as the potential of the prognosis of rectal gland cancer biomarkers. Our study constructed a prognostic model of rectal adenocarcinoma consisting of three related m6A lncRNAs: linc00702, ac106900.1 and al583785.1. CONCLUSION: The model has been validated as a potential prognostic biomarker for rectal cancer in multiple dimensions, aiming to provide clinicians with an indicator to assess the duration of straight adenocarcinoma. This enables early detection of rectal cancer and offers a promising target for immunotherapy. Show more
Keywords: Long noncoding RNA (lncRNAs), rectal adenocarcinoma, prognostic model, m6A, immune microenvironment
DOI: 10.3233/CBM-230123
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Zhao, Zhi Yi | Cao, Yin | Wang, Hong Liang | Liu, Ling Yun
Article Type: Research Article
Abstract: OBJECTIVES: We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC. METHODS: We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram …for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507. RESULTS: Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1–penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group’s OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P = 5.678e-07) was poorer than that of low-risk groups’ (HR, 1.675; 95% CI, 1.037 to 2.713; P = 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p = 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score. CONCLUSIONS: The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC. Show more
Keywords: Competing endogenous RNA, prognosis, nomogram, bladder cancer
DOI: 10.3233/CBM-230216
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Abd ELhafeez, Ahmed Saeed | Ghanem, Hala Mostafa | Swellam, Menha | Taha, AlShaimaa Mohamed
Article Type: Research Article
Abstract: BACKGROUND: FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. OBJECTIVE: The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. METHODS: This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The …expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs’ associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. RESULTS: The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC’s stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p , respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. CONCLUSIONS: The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC. Show more
Keywords: Bioinformatics, diagnostic, EGFR, KRAS, risk factor
DOI: 10.3233/CBM-230396
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-21, 2023
Authors: Dang, Tianfeng | Yu, Jieqing | Yu, Yanqing | Jiang, Junjie | Shi, Yang | Yu, Simin | Peng, Congli | Min, Xiang | Xiong, Yuanping | Long, Ping | Zhou, Wensheng | Dai, Daofeng
Article Type: Research Article
Abstract: GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly …inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies. Show more
Keywords: Apoptosis, cell proliferation, molecular targets, programmed cell death, thyroid cancer
DOI: 10.3233/CBM-230220
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-12, 2023
Authors: Záveský, Luděk | Jandáková, Eva | Weinberger, Vít | Minář, Luboš | Kohoutová, Milada | Slanař, Ondřej
Article Type: Research Article
Abstract: BACKGROUND: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease. OBJECTIVE: Evaluation of novel long non-coding RNAs biomarkers for breast cancer. METHODS: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics. RESULTS: The …results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality. CONCLUSIONS: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies. Show more
Keywords: Breast cancer, GNG12-AS1, clinical outcomes, long non-coding RNAs, MAGI2-AS3, MEG3, NRSN2-AS1, PTENP1, UCA1
DOI: 10.3233/CBM-230259
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-18, 2024
Authors: Li, Thomas Z. | Xu, Kaiwen | Chada, Neil C. | Chen, Heidi | Knight, Michael | Antic, Sanja | Sandler, Kim L. | Maldonado, Fabien | Landman, Bennett A. | Lasko, Thomas A.
Article Type: Research Article
Abstract: BACKGROUND: Large community cohorts are useful for lung cancer research, allowing for the analysis of risk factors and development of predictive models. OBJECTIVE: A robust methodology for (1) identifying lung cancer and pulmonary nodules diagnoses as well as (2) associating multimodal longitudinal data with these events from electronic health record (EHRs) is needed to optimally curate cohorts at scale. METHODS: In this study, we leveraged (1) SNOMED concepts to develop ICD-based decision rules for building a cohort that captured lung cancer and pulmonary nodules and (2) clinical knowledge to define time windows for …collecting longitudinal imaging and clinical concepts. We curated three cohorts with clinical data and repeated imaging for subjects with pulmonary nodules from our Vanderbilt University Medical Center. RESULTS: Our approach achieved an estimated sensitivity 0.930 (95% CI: [0.879, 0.969]), specificity of 0.996 (95% CI: [0.989, 1.00]), positive predictive value of 0.979 (95% CI: [0.959, 1.000]), and negative predictive value of 0.987 (95% CI: [0.976, 0.994]) for distinguishing lung cancer from subjects with SPNs. CONCLUSION: This work represents a general strategy for high-throughput curation of multi-modal longitudinal cohorts at risk for lung cancer from routinely collected EHRs. Show more
Keywords: Pulmonary nodules, lung cancer, EHR mining, multimodal longitudinal cohorts
DOI: 10.3233/CBM-230340
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
Authors: Xie, Kai | Wang, Bin | Pang, Pei | Li, Guangbin | Yang, Qianqian | Fang, Chen | Jiang, Wei | Feng, Yu | Ma, Haitao
Article Type: Research Article
Abstract: BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of …the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P < 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification. Show more
Keywords: Disulfidptosis, lung adenocarcinoma, ACTN4, immune infiltration, therapeutic target
DOI: 10.3233/CBM-230276
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Liu, Yang | Pang, Zhongqi | Wang, Jianshe | Wang, Jinfeng | Ji, Bo | Xu, Yidan | He, Jiaxin | Zhang, Lu | Han, Yansong | Shen, Linkun | Xu, Wanhai | Ren, Minghua
Article Type: Research Article
Abstract: BACKGROUND: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed. OBJECTIVE: To predict the value of m6A-related genes in prognosis and immunity in BC. METHODS: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients. RESULTS: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. …Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC. Show more
Keywords: N6-methyladenosine, bladder cancer, prognosis, immunotherapy, m6A score
DOI: 10.3233/CBM-230286
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2024
Authors: Li, Wuping | Yao, Ruizhe | Yu, Nasha | Zhang, Weiming
Article Type: Research Article
Abstract: BACKGROUND: Therapies for diffuse large B-cell lymphoma (DLBCL) are limited due to the diverse gene expression profiles and complicated immune microenvironments, making it an aggressive lymphoma. Beyond this, researches have shown that ferroptosis contributes to tumorigenesis, progression, and metastasis. We thus are interested to dissect the connection between ferroptosis and disease status of DLBCL. We aim at generating a valuable prognosis gene signature for predicting the status of patients of DLBCL, with focus on ferroptosis-related genes (FRGs). OBJECTIVE: To examine the connection between ferroptosis-related genes (FRGs) and clinical outcomes in DLBCL patients based on public datasets. …METHODS: An expression profile dataset for DLBCL was downloaded from GSE32918 (https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc=gse32918 ), and a ferroptosis-related gene cluster was obtained from the FerrDb database (http://www. zhounan.org/ferrdb/ ). A prognostic signature was developed from this gene cluster by applying a least absolute shrinkage and selection operator (LASSO) Cox regression analysis to GSE32918, followed by external validation. Its effectiveness as a biomarker and the prognostic value was determined by a receiver operator characteristic curve mono factor analysis. Finally, functional enrichment was evaluated by the package Cluster Profiler of R. RESULTS: Five ferroptosis-related genes (FRGs) (GOP1 , GPX2 , SLC7A5 , ATF4 , and CXCL2 ) associated with DLBCL were obtained by a multivariate analysis. The prognostic power of these five FRGs was verified by TCGA (https://xenabrowser.net/datapages/?dataset=TCGA.DLBC.sampleMap%2FHiSeqV2_PANCAN&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A44 ) and GEO (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse 32918 ) datasets, with ROC analyses. KEGG and GO analyses revealed that upregulated genes in the high-risk group based on the gene signature were enriched in receptor interactions and other cancer-related pathways, including pathways related to abnormal metabolism and cell differentiation. CONCLUSION: The newly developed signature involving GOP1 , GPX2 , SLC7A5 , ATF4 , and CXCL2 has the potential to serve as a prognostic biomarker. Furthermore, our results provide additional support for the contribution of ferroptosis to DLBCL. Show more
Keywords: GOP1, GPX2, SLC7A5, ATF4, CXCL2, ferroptosis-related genes, DLBCL
DOI: 10.3233/CBM-230325
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Wang, Tianxiang | Qian, Luxi | Zhang, Pingchuan | Du, Mingyu | Wu, Jing | Peng, Fanyu | Yao, Chengyun | Yin, Rong | Yin, Li | He, Xia
Article Type: Research Article
Abstract: INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to …screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target. Show more
Keywords: HNSCC, GINS2, RRM2, proliferation, apoptosis
DOI: 10.3233/CBM-230337
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Priya C V, Lakshmi | V G, Biju | B R, Vinod | Ramachandran, Sivakumar
Article Type: Research Article
Abstract: BACKGROUND: Breast cancer is one of the leading causes of death in women worldwide. Histopathology analysis of breast tissue is an essential tool for diagnosing and staging breast cancer. In recent years, there has been a significant increase in research exploring the use of deep-learning approaches for breast cancer detection from histopathology images. OBJECTIVE: To provide an overview of the current state-of-the-art technologies in automated breast cancer detection in histopathology images using deep learning techniques. METHODS: This review focuses on the use of deep learning algorithms for the detection and classification of breast …cancer from histopathology images. We provide an overview of publicly available histopathology image datasets for breast cancer detection. We also highlight the strengths and weaknesses of these architectures and their performance on different histopathology image datasets. Finally, we discuss the challenges associated with using deep learning techniques for breast cancer detection, including the need for large and diverse datasets and the interpretability of deep learning models. RESULTS: Deep learning techniques have shown great promise in accurately detecting and classifying breast cancer from histopathology images. Although the accuracy levels vary depending on the specific data set, image pre-processing techniques, and deep learning architecture used, these results highlight the potential of deep learning algorithms in improving the accuracy and efficiency of breast cancer detection from histopathology images. CONCLUSION: This review has presented a thorough account of the current state-of-the-art techniques for detecting breast cancer using histopathology images. The integration of machine learning and deep learning algorithms has demonstrated promising results in accurately identifying breast cancer from histopathology images. The insights gathered from this review can act as a valuable reference for researchers in this field who are developing diagnostic strategies using histopathology images. Overall, the objective of this review is to spark interest among scholars in this complex field and acquaint them with cutting-edge technologies in breast cancer detection using histopathology images. Show more
Keywords: Computer-aided detection, breast cancer, histopathology images, deep learning, Convolutional Neural Network (CNN)
DOI: 10.3233/CBM-230251
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-25, 2024
Authors: Zhang, Yuke | Liu, Kai | Wang, Jianzhong
Article Type: Research Article
Abstract: BACKGROUND: Osteosarcoma (OS) is a relatively rare malignant bone tumor in teenagers; however, its molecular mechanisms are not yet understood comprehensively. OBJECTIVE: The study aimed to use necroptosis-related genes (NRGs) and their relationships with immune-related genes to construct a prognostic signature for OS. METHODS: TARGET-OS was used as the training dataset, and GSE 16091 and GSE 21257 were used as the validation datasets. Univariate regression, survival analysis, and Kaplan-Meier curves were used to screen for hub genes. The immune-related targets were screened using immune infiltration assays and immune checkpoints. The results were validated …using nomogram and decision curve analyses (DCA). RESULTS: Using univariate Cox regression analysis, TNFRSF1A was screened from 14 NRGs as an OS prognostic signature. Functional enrichment was analyzed based on the median expression of TNFRSF1A. The prognosis of the TNFRSF1A low-expression group in the Kaplan-Meier curve was notably worse. Immunohistochemistry analysis showed that the number of activated T cells and tumor purity increased considerably. Furthermore, the immune checkpoint lymphocyte activation gene 3 (LAG-3) is a possible target for intervention. The nomogram accurately predicted 1-, 3-, and 5-year survival rates. DCA validated the model (C = 0.669). Conclusion: TNFRSF1A can be used to elucidate the potential relationship between the immune microenvironment and NRGs in OS pathogenesis. Show more
Keywords: Osteosarcoma, necroptosis, tumor immune microenvironment, TNFRSF1A, prognosis
DOI: 10.3233/CBM-230086
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2023
Authors: Zhu, Liucun | Yuan, Fa | Wang, Xue | Zhu, Rui | Guo, Wenna
Article Type: Research Article
Abstract: Cuproptosis a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among DNA-methylation located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating …characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients. Show more
Keywords: Lower-grade glioma, cuproptosis, DNA-methylation, tumor microenvironment, immune checkpoint inhibitors
DOI: 10.3233/CBM-230341
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Wen, Yixin | Xu, Feng | Zhang, Hui
Article Type: Research Article
Abstract: BACKGROUND: Circular RNAs (circRNAs) perform key regulatory functions in osteosarcoma (OS) tumorigenesis. In this study, we aimed to explore the detailed action mechanisms of circ_0049271 in OS progression. METHODS: Cell colony formation, cell counting kit-8, and transwell assays were performed to assess the proliferation and invasion of OS cells. Quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine the expression levels of polymerase 1 and transcript release factor (PTRF), microRNA (miR)-1197, and circ_0049271 in OS cells. Furthermore, RNA immunoprecipitation and dual luciferase assays were conducted to explore the targeted relationships among PTRF …, miR-1197 , and circ_0049271 . Finally, a tumor formation assay was conducted to determine the effects of circ_0049271 on in vivo tumor growth in mice. RESULTS: High expression levels of miR-1197 and low levels of circ_0049271 and PTRF were observed in OS cells. circ _0049271 targeted miR-1197 to mediate PTRF expression. Moreover, the proliferation and invasion of OS cells were repressed by circ_0049271 or PTRF overexpression and increased by miR-1197 upregulation. Enforced circ_0049271 also impeded tumor growth in vivo . Upregulation of miR-1197 reversed the antitumor effects of circ_0049271 on OS progression in vitro ; however, PTRF overexpression attenuated the cancer-promoting effects of miR-1197 on OS in vitro . CONCLUSIONS: Our findings revealed that circ_0049271 targeted the miR-1197/PTRF axis to attenuate the malignancy of OS, suggesting a potential target for its clinical treatment. Show more
Keywords: Osteosarcoma, circRNA, circ_0049271, miR-1197, PTRF
DOI: 10.3233/CBM-230191
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Horackova, Klara | Vocka, Michal | Lopatova, Sarka | Zemankova, Petra | Kleibl, Zdenek | Soukupova, Jana
Article Type: Research Article
Abstract: BACKGROUND: Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. OBJECTIVE: The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. METHODS: We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival …were analysed. RESULTS: The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90–3.26; p = 4.14 × 10 - 11 ) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04–1.07; p = 2 × 10 - 6 ), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32–0.60; p = 1.95 × 10 - 7 ) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48–0.87; p = 4.53 × 10 - 3 ). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01–2.38; p = 0.046). CONCLUSIONS: Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC. Show more
Keywords: Ovarian cancer, long-term survival, PRDM1, BRCA1, biomarker
DOI: 10.3233/CBM-230358
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-5, 2024
Authors: Kimura, Nozomu | Tsukita, Yoko | Ebina-Shibuya, Risa | Miyauchi, Eisaku | Yamada, Mitsuhiro | Narita, Daisuke | Saito, Ryota | Inoue, Chihiro | Fujino, Naoya | Ichikawa, Tomohiro | Tamada, Tsutomu | Sugiura, Hisatoshi
Article Type: Research Article
Abstract: BACKGROUND: Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable. OBJECTIVE: This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples. METHODS: Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines. RESULTS: Nineteen patients were enrolled. The proportions …of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P = 0.0032; median 1.2%-vs-0.3%, P = 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P = 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P = 0.0002). CONCLUSIONS: We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC. Show more
Keywords: Combination of chemotherapy and immune checkpoint inhibitor, NSCLC, natural killer cells, CD4 + cells, CXCL10
DOI: 10.3233/CBM-230301
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
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