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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: Pei, Wenceng | Jiang, Minren | Liu, Haiyan | Song, Jiahong | Hu, Jian
Article Type: Research Article
Abstract: BACKGROUND: Liver hepatocellular cancer (LIHC) and stomach adenocarcinoma (STAD) are common malignancies with high lethal ratios worldwide. Great progress has been achieved by using diverse therapeutic strategies; however, these diseases still have an unfavourable prognosis. Ferroptosis inducer drugs, unlike apoptosis-related drugs, can overcome the resistance to cancer therapy caused by traditional chemicals. However, the relationship between overall survival (OS) and ferroptosis-related genes, as well as the mechanisms involved, are largely unclear. METHODS: The expression levels of AIFM2, GPX4, ACSL4, FTH1, NOS1, and PTGS2 in LIHC and STAD were obtained from UALCAN. The correlations of OS with …these gene expression levels were obtained using the Kaplan-Meier Plotter database. The OS associated with genetic mutations of those genes compared to that of unchanged genes was analysed using the TIMER website. GO and KEGG enrichment analyses of ferroptosis-related genes and their coexpressed genes in LIHC and STAD were conducted using the STRING and DAVID databases. The relationship of PTGS2 and ACSL4 to immune cell infiltration was analysed using the TIMER website. The viability and GPX5 expression levels in LIHC cells treated with RSL3 and As 2 O 3 were detected by MTT methods and western blotting, respectively. RESULTS: Our results showed that GPX4, FTH1 and AIFM2 were overexpressed in LIHC and STAD. High levels of GPX4, FTH1 and AIFM2 were prominently correlated with better prognosis in LIHC. However, GPX and FTH1 in STAD did not show significant correlations with OS. AIFM2 in STAD had the opposite trend with OS compared with that in LIHC. Moreover, a high mutation rate of these genes (35.74%) was also observed in LIHC patients, and genetic mutation of these genes was correlated with shorter OS. In contrast, the genetic mutation of these genes did not change OS in STAD. Enrichment analysis showed that the respiratory electron transport chain, cell chemotaxis and T-cell migration were related to ferroptosis. ASCL4 and PTGS2 coexpressed with cytokines associated with immune cell infiltration. Compared to RSL3 or As 2 O 3 alone, As2O3 plus RSL3 significantly inhibited the growth of Huh7 cells. GPX4 was downregulated to an undetectable level when in combination with RSL3. CONCLUSIONS: Our results indicated that ferroptosis-related genes might play an important role in LIHC and STAD and might be risk factors for overall survival in LIHC and STAD. Show more
Keywords: Liver hepatocellular cancer, stomach adenocarcinoma, ferroptosis, prognosis, enrichment analysis
DOI: 10.3233/CBM-230114
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2023
Authors: Paez, Rafael | Rowe, Dianna J. | Deppen, Stephen A. | Grogan, Eric L. | Kaizer, Alexander | Bornhop, Darryl J. | Kussrow, Amanda K. | Barón, Anna E. | Maldonado, Fabien | Kammer, Michael N.
Article Type: Research Article
Abstract: BACKGROUND: Assessing the clinical utility of biomarkers is a critical step before clinical implementation. The reclassification of patients across clinically relevant subgroups is considered one of the best methods to estimate clinical utility. However, there are important limitations with this methodology. We recently proposed the intervention probability curve (IPC) which models the likelihood that a provider will choose an intervention as a continuous function of the probability, or risk, of disease. OBJECTIVE: To assess the potential impact of a new biomarker for lung cancer using the IPC. METHODS: The IPC derived from the …National Lung Screening Trial was used to assess the potential clinical utility of a biomarker for suspected lung cancer. The summary statistics of the change in likelihood of intervention over the population can be interpreted as the expected clinical impact of the added biomarker. RESULTS: The IPC analysis of the novel biomarker estimated that 8% of the benign nodules could avoid an invasive procedure while the cancer nodules would largely remain unchanged (0.1%). We showed the benefits of this approach compared to traditional reclassification methods based on thresholds. CONCLUSIONS: The IPC methodology can be a valuable tool for assessing biomarkers prior to clinical implementation. Show more
Keywords: Biomarkers, clinical utility, Intervention Probability Curve, indeterminate pulmonary nodule, net reclassification index
DOI: 10.3233/CBM-230054
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2023
Authors: Li, Shan | Li, Ting | Shi, Yan-Qing | Xu, Bin-Jie | Deng, Yu-Yong | Sun, Xu-Guang
Article Type: Research Article
Abstract: BACKGROUND: Our study aimed to investigate the Hub genes and their prognostic value in colorectal cancer (CRC) via bioinformatics analysis. METHODS: The data set of colorectal cancer was downloaded from the GEO database (GSE21510, GSE110224 and GSE74602) for differential expression analysis using the GEO2R tool. Hub genes were screened by protein-protein interaction (PPI) comprehensive analysis. GEPIA was used to verify the expression of Hub genes and evaluate its prognostic value. The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database. The cBioPortal was used to analyze the type and frequency …of Hub gene mutations, and the effects of mutation on the patients’ prognosis. The TIMER database was used to study the correlation between Hub genes and immune infiltration in CRC. Gene set enrichment analysis (GSEA) was used to explore the biological function and signal pathway of the Hub genes and corresponding co-expressed genes. RESULTS: We identified 346 differentially expressed genes (DEGs), including 117 upregulated and 229 downregulated. Four Hub genes (AURKA, CCNB1, EXO1 and CCNA2) were selected by survival analysis and differential expression validation. The protein and mRNA expression levels of AURKA, CCNB1, EXO1 and CCNA2 were higher in CRC tissues than in adjacent tissues. There were varying degrees of immune cell infiltration and gene mutation of Hub genes, especially B cells and CD8+ T cells. The results of GSEA showed that Hub genes and their co-expressed genes mainly participated in chromosome segregation, DNA replication, translational elongation and cell cycle. CONCLUSION: Overexpression of AURKA, CCNB1, CCNA2 and EXO1 had a better prognosis for CRC and this effect was correlation with gene mutation and infiltration of immune cells. Show more
Keywords: Colorectal cancer, bioinformatics analysis, Hub genes, prognosis
DOI: 10.3233/CBM-230113
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-19, 2024
Authors: S, Vinoth | Balasubramanian, Satheeswaran | Perumal, Ekambaram | Santhakumar, Kirankumar
Article Type: Research Article
Abstract: BACKGROUND: Clear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent types of kidney cancer. Unravelling the genes responsible for driving cellular changes and the transformation of cells in ccRCC pathogenesis is a complex process. OBJECTIVE: In this study, twelve microarray ccRCC datasets were chosen from the gene expression omnibus (GEO) database and subjected to integrated analysis. METHODS: Through GEO2R analysis, 179 common differentially expressed genes (DEGs) were identified among the datasets. The common DEGs were subjected to functional enrichment analysis using ToppFun followed by construction of protein-protein interaction network (PPIN) …using Cytoscape. Clusters within the DEGs PPIN were identified using the Molecular Complex Detection (MCODE) Cytoscape plugin. To identify the hub genes, the centrality parameters degree, betweenness, and closeness scores were calculated for each DEGs in the PPIN. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) was utilized to validate the relative expression levels of hub genes in the normal and ccRCC tissues. RESULTS: The common DEGs were highly enriched in Hypoxia-inducible factor (HIF) signalling and metabolic reprogramming pathways. VEGFA , CAV1 , LOX , CCND1 , PLG , EGF , SLC2A1 , and ENO2 were identified as hub genes. CONCLUSION: Among 8 hub genes, only the expression levels of VEGFA , LOX , CCND1 , and EGF showed a unique expression pattern exclusively in ccRCC on compared to other type of cancers. Show more
Keywords: Kidney cancer, hypoxia, metabolic reprogramming, hub genes, cancer biomarker
DOI: 10.3233/CBM-230271
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Zhang, Zhixiang | Guo, Jipeng | Gong, Chongwen | Wu, Sai | Sun, Yanlei
Article Type: Research Article
Abstract: BACKGROUND: N6-methyladenosine (m6 A) modification has been associated with non-small cell lung cancer (NSCLC) tumorigenesis. OBJECTIVES: This study aimed to determine the functions of Vir-like m6 A methyltransferase-associated (KIAA1429) and relaxin family peptide receptor 1 (RXFP1) in NSCLC. METHODS: A quantitative real-time polymerase chain reaction was used to analyze the mRNA levels of KIAA1429 and RXFP1 in NSCLC. After silencing KIAA1429 or RXFP1 in NSCLC cells, changes in the malignant phenotypes of NSCLC cells were assessed using cell counting kit-8, colony formation, and transwell assays. Finally, the m6 A modification of RXFP1 mediated …by KIAA1429 was confirmed using luciferase, methylated RNA immunoprecipitation, and western blot assays. RESULTS: KIAA1429 and RXFP1 were upregulated and downregulated in NSCLC, respectively. Silencing of KIAA1429 attenuated the viability, migration, and invasion of NSCLC cells, whereas silencing of RXFP1 showed the opposite function in NSCLC cells. Moreover, RXFP1 expression was inhibited by KIAA1429 via m6 A-modification. Therefore, silencing RXFP1 reversed the inhibitory effect of KIAA1429 knockdown in NSCLC cells. CONCLUSION: Our findings confirmed that the KIAA1429/RXFP1 axis promotes NSCLC tumorigenesis. This is the first study to reveal the inhibitory function of RXFP1 in NSCLC via KIAA1429-mediated m6 A-modification. These findings may help identify new biomarkers for targeted NSCLC therapy. Show more
Keywords: N6-methyladenosine, KIAA1429, RXFP1, non-small cell lung cancer
DOI: 10.3233/CBM-230188
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Kim, Roger Y.
Article Type: Research Article
Abstract: Pulmonary nodules are ubiquitously found on computed tomography (CT) imaging either incidentally or via lung cancer screening and require careful diagnostic evaluation and management to both diagnose malignancy when present and avoid unnecessary biopsy of benign lesions. To engage in this complex decision-making, clinicians must first risk stratify pulmonary nodules to determine what the best course of action should be. Recent developments in imaging technology, computer processing power, and artificial intelligence algorithms have yielded radiomics-based computer-aided diagnosis tools that use CT imaging data including features invisible to the naked human eye to predict pulmonary nodule malignancy risk and are designed …to be used as a supplement to routine clinical risk assessment. These tools vary widely in their algorithm construction, internal and external validation populations, intended-use populations, and commercial availability. While several clinical validation studies have been published, robust clinical utility and clinical effectiveness data are not yet currently available. However, there is reason for optimism as ongoing and future studies aim to target this knowledge gap, in the hopes of improving the diagnostic process for patients with pulmonary nodules. Show more
Keywords: Radiomics, artificial intelligence, lung cancer, risk stratification, pulmonary nodule
DOI: 10.3233/CBM-230360
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Karataş, Fatih | Acat, Murat | Karatas, Hatice Gulsah | İnci, Fatih | Dikiş, Özlem Sengören
Article Type: Research Article
Abstract: BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for …age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p = 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p = 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p = 0.002). In the multivariate regression analysis; Decorin < 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p = 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment. Show more
Keywords: Non small cell, lung cancer, decorin, biglycan, TGF-B1
DOI: 10.3233/CBM-230238
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2023
Authors: Singh, Varsha | Katiyar, Amit | Malik, Prabhat | Kumar, Sunil | Mohan, Anant | Singh, Harpreet | Jain, Deepali
Article Type: Research Article
Abstract: OBJECTIVES: Significant progress has been made in the treatment of patients with pulmonary adenocarcinoma (ADCA) based on molecular profiling. However, no such molecular target exists for squamous cell carcinoma (SQCC). An exome sequence may provide new markers for personalized medicine for lung cancer patients of all subtypes. The current study aims to discover new genetic markers that can be used as universal biomarkers for non-small cell lung cancer (NSCLC). METHODS: WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was performed using Illumina HiSeq 2000. Variant calling was performed using GATK HaplotypeCaller and then …the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. The clinical impact of somatic variants in cancer was assessed using cancer archives. Somatic variants were further prioritized using a knowledge-driven variant interpretation approach. Sanger sequencing was used to validate functionally important variants. RESULTS: We identified 24 rare single-nucleotide variants (SNVs) including 17 non-synonymous SNVs, and 7 INDELs in 18 genes possibly linked to lung carcinoma. Variants were classified as known somatic (n = 10), deleterious (n = 8), and variant of uncertain significance (n = 6). We found TBP and MPRIP genes exclusively associated with ADCA subtypes, FBOX6 with SQCC subtypes and GPRIN2, KCNJ18 and TEKT4 genes mutated in all the patients. The Sanger sequencing of 10 high-confidence somatic SNVs showed 100% concordance in 7 genes, and 80% concordance in the remaining 3 genes. CONCLUSIONS: Our bioinformatics analysis identified KCNJ18, GPRIN2, TEKT4, HRNR, FOLR3, ESSRA, CTBP2, MPRIP, TBP, and FBXO6 may contribute to progression in NSCLC and could be used as new biomarkers for the treatment. The mechanism by which GPRIN2, KCNJ12, and TEKT4 contribute to tumorigenesis is unclear, but our results suggest they may play an important role in NSCLC and it is worth investigating in future. Show more
Keywords: Non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma, biomarker, whole-exome sequencing
DOI: 10.3233/CBM-220211
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-18, 2023
Authors: Zhu, Ziwen | Jiang, Weizhen | Zhou, Danhong | Zhu, Weidong | Chen, Cheng
Article Type: Research Article
Abstract: BACKGROUND: In clinical practice, preoperative identification of mixed ground-glass opacity (mGGO) nodules with micropapillary component (MPC) to facilitate the implementation of individualized therapeutic strategies and avoid unnecessary surgery is increasingly important OBJECTIVE: This study aimed to build a predictive model based on clinical and radiological variables for the early identification of MPC in lung adenocarcinoma presenting as mGGO nodules. METHODS: The enrolled 741 lung adenocarcinoma patients were randomly divided into a training cohort and a validation cohort (3:1 ratio). The pathological specimens and preoperative images of malignant mGGO nodules from the study subjects …were retrospectively reviewed. Furthermore, in the training cohort, selected clinical and radiological variables were utilized to construct a predictive model for MPC prediction. RESULTS: The MPC was found in 228 (43.3%) patients in the training cohort and 72 (41.1%) patients in the validation cohort. Based on the predictive nomogram, the air bronchogram was defined as the most dominant independent risk factor for MPC of mGGO nodules, followed by the maximum computed tomography (CT) value (> 200), adjacent to pleura, gender (male), and vacuolar sign. The nomogram demonstrated good discriminative ability with a C-index of 0.783 (95%[CI] 0.744–0.822) in the training cohort and a C-index of 0.799 (95%[CI] 0.732–0.866) in the validation cohort Additionally, by using the bootstrapping method, this predictive model calculated a corrected AUC of 0.774 (95% CI: 0.770–0.779) in the training cohort. CONCLUSIONS: This study proposed a predictive model for preoperative identification of MPC in known lung adenocarcinomas presenting as mGGO nodules to facilitate individualized therapy. This nomogram model needs to be further externally validated by subsequent multicenter studies. Show more
Keywords: Mixed ground-glass opacity (mGGO), micropapillary component (MPC), lung adenocarcinoma, predictive model, nomogram
DOI: 10.3233/CBM-230104
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Chen, Cheng | Wang, Caiming | Liu, Wei | Chen, Jiacheng | Chen, Liang | Luo, Xiangxiang | Wu, Jincai
Article Type: Research Article
Abstract: BACKGROUND: Cms1 ribosomal small subunit homolog (CMSS1) is an RNA-binding protein that may play an important role in tumorigenesis and development. OBJECTIVE: RNA-seq data from the GEPIA database and the UALCAN database were used to analyze the expression of CMSS1 in liver hepatocellular carcinoma (LIHC) and its relationship with the clinicopathological features of the patients. METHODS: LinkedOmics was used to identify genes associated with CMSS1 expression and to identify miRNAs and transcription factors significantly associated with CMSS1 by GSEA. RESULTS: The expression level of CMSS1 in hepatocellular carcinoma tissues was …significantly higher than that in normal tissues. In addition, the expression level of CMSS1 in advanced tumors was significantly higher than that in early tumors. The expression level of CMSS1 was higher in TP53-mutated tumors than in non-TP53-mutated tumors. CMSS1 expression levels were strongly correlated with disease-free survival (DFS) and overall survival (OS) in patients with LIHC, and high CMSS1 expression predicted poorer OS (P < 0.01) and DFS (P < 0.01). Meanwhile, our results suggested that CMSS1 is associated with the composition of the immune microenvironment of LIHC. CONCLUSIONS: The present study suggests that CMSS1 is a potential molecular marker for the diagnosis and prognostic of LIHC. Show more
Keywords: CMSS1, hepatocellular carcinoma, . bioinformatics, diagnosis, prognosis
DOI: 10.3233/CBM-230209
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2023
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