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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
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