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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: Bongolo, Christian Cedric | Thokerunga, Erick | Fidele, Nyimi Bushabu | Souraka, Tapara Dramani Maman | Kisembo, Peter | Rugera, Simon Peter | Worley, Paul F. | Tu, Jian-Cheng
Article Type: Research Article
Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. OBJECTIVE: To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. METHODS: Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver …cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. RESULTS: LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo . CONCLUSION: The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases. Show more
Keywords: Hepatocellular carcinoma, long non-coding RNA, proliferation, invasion, metastasis
DOI: 10.3233/CBM-220033
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 245-256, 2022
Authors: Kabekkodu, Shama Prasada | Chakrabarty, Sanjiban | Varghese, Vinay Koshy | Ghosh, Supriti | Radhakrishnan, Raghu | Mallya, Sandeep P. | Kudva, Adarsh
Article Type: Research Article
Abstract: PURPOSE: Aberrant DNA methylation plays a crucial role in oral carcinogenesis. Our previous study demonstrated hypermethylation of DAPK1, LRPPRC, RAB6C, and ZNF471 promoters in patients with tongue squamous cell carcinoma compared with normal samples. Methylation profiling using salivary DNA is considered a non-invasive alternative to tissue samples. Hence, the present study tested the DNA methylation status of these four promoters as indicators of oral cancer progression. METHODS: We performed the bisulfite-based targeted next-generation sequencing of four candidate genes in saliva and tissue DNA from normal, premalignant, and squamous cell carcinoma subjects. The clinicopathological association, …diagnostic, and prognostic utility of aberrant DNA methylation were evaluated using the TCGA-HNSCC dataset. Using the Xgboost algorithm and logistic regression, CpG sites were prioritized, and Receiver Operating Characteristic was generated. By Log-rank test and Kaplan-Meier (KM) curves, an association between methylation and overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) were computed. RESULTS: We identified all four genes as significantly hypermethylated in premalignant and malignant samples compared with normal samples. The methylation levels were comparable between saliva and tissue samples with an r-value of 0.6297 to 0.8023 and 0.7823 to 0.9419 between premalignant tissue vs. saliva and OC vs. saliva, respectively. We identified an inverse correlation between DAPK1, LRPPRC, RAB6C, and ZNF471 promoter methylation with their expression. A classifier of 8 differentially methylated CpG sites belonging to DAPK1 , RAB6C , and ZNF471 promoters was constructed, showing an AUC of 0.984 to differentiate tumors from normal samples. The differential methylation status of DAPK1, LRPPRC, and ZNF71 promoters was prognostically important. Abnormal expression of all four genes was associated with immune infiltration. CONCLUSIONS: Thus, methylation analysis of these candidate CpG sites from saliva can be helpful as a non-invasive tool for the clinical management of OC. Show more
Keywords: DNA hypermethylation, saliva, non-invasive marker, oral squamous cell carcinoma, bisulfite targeted next-generation sequencing, prognosis
DOI: 10.3233/CBM-220028
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 257-268, 2022
Authors: Saeednejad Zanjani, Leili | Vafaei, Somayeh | Abolhasani, Maryam | Fattahi, Fahimeh | Madjd, Zahra
Article Type: Research Article
Abstract: METHODS: Talin-1 protein was demonstrated as a potential prognostic marker in renal cell carcinoma (RCC) using bioinformatics analysis. We, therefore, examined the protein expression levels and prognostic significance of Talin-1 with a clinical follow-up in a total of 269 tissue specimens from three important subtypes of RCC and 30 adjacent normal samples using immunohistochemistry. Then, we used combined analysis with B7-H3 to investigate higher prognostic values. RESULTS: The results showed that high membranous and cytoplasmic expression of Talin-1 was significantly associated with advanced nucleolar grade, microvascular invasion, histological tumor necrosis, and invasion to Gerota’s fascia in …clear cell RCC (ccRCC). In addition, high membranous and cytoplasmic expression of Talin-1 was found to be associated with significantly poorer disease-specific survival (DSS) and progression-free survival (PFS). Moreover, increased cytoplasmic expression of Talin-1 High /B7-H3 High compared to the other phenotypes was associated with tumor aggressiveness and progression of the disease, and predicted a worse clinical outcome, which may be an effective biomarker to identify ccRCC patients at high risk of recurrence and metastasis. CONCLUSIONS: Collectively, these observations indicate that Talin-1 is an important molecule involved in the spread and progression of ccRCC when expressed particularly in the cytoplasm and may serve as a novel prognostic biomarker in this subtype. Furthermore, a combined analysis of Talin-1/B7-H3 indicated an effective biomarker to predict the progression of disease and prognosis in ccRCC. Show more
Keywords: Talin-1, bioinformatics, ccRCC, B7-H3, tissue microarray (TMA)
DOI: 10.3233/CBM-220018
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 269-292, 2022
Authors: Gao, Zhenhua | Chen, Cheng | Gu, Peng | Chen, Jianheng | Liu, Xiaodong | Shen, Jihong
Article Type: Research Article
Abstract: BACKGROUND: Autophagy-related genes and immune-related genes contribute significantly to the initiation and prognosis of bladder cancer (BLCA). OBJECTIVE: We aimed to explore differentially expressed autophagy-related genes (DEARGs) and immune-related genes (DEIRGs) in BLCA to create a prognostic risk assessment model and gain some insights into BLCA’s molecular underpinnings. METHODS: The prognostic DEARGs and DEIRGs were evaluated for BLCA through The Cancer Genome Atlas (TCGA) database (n = 399) and GSE13507 dataset (n = 165). The BLCA risk model was constructed and verified. The …immune score, stromal score, and estimate score in different risk groups were calculated by the ESTIMATE algorithm. Immune infiltration levels were assessed by a single sample gene set enrichment analysis (GSEA) algorithm. RESULTS: In the risk model, AURKA, ACTC1, MYLK, PDGFD, PDGFRA and TNC were significantly associated with the overall survival. The pathways in cancer, T cell receptor signaling pathway and B cell receptor signaling pathway were significantly gathered in the high-risk group. Moreover, the risk score was significantly correlated with infiltrating immune cells, expression of critical immune checkpoints and mismatch repair genes including MSH6, MLH1, and MSH2. CONCLUSIONS: In this study, three DEARGs (AURKA, ACTC1, MYLK) and three DEIRGs (PDGFD, PDGFRA, TNC) were demonstrated to be potential prognostic biomarkers for BLCA patients through bioinformatics methods, which might be novel therapeutic targets and prognostic markers for BLCA, in follow up studies, we will combine experiments to verify this. Show more
Keywords: Bladder cancer, autophagy, immune, risk model, prognosis
DOI: 10.3233/CBM-220058
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 293-303, 2022
Authors: Zi, Quan | Cui, Hanwei | Liang, Wei | Chi, Qingjia
Article Type: Research Article
Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Due to the lack of specific characteristics in the early stage of the disease, patients are usually diagnosed in the advanced stage of disease progression. OBJECTIVE: This study used machine learning algorithms to identify key genes in the progression of hepatocellular carcinoma and constructed a prediction model to predict the survival risk of HCC patients. METHODS: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differential expression analysis and COX …proportional-hazards model participated in the identification of survival-related genes. K-Means, Random forests, and LASSO regression are involved in identifying novel subtypes of HCC and screening key genes. The prediction model was constructed by deep neural networks (DNN), and Gene Set Enrichment Analysis (GSEA) reveals the metabolic pathways where key genes are located. RESULTS: Two subtypes were identified with significantly different survival rates (p < 0.0001, AUC = 0.720) and 17 key genes associated with the subtypes. The accuracy rate of the deep neural network prediction model is greater than 93.3%. The GSEA analysis found that the survival-related genes were significantly enriched in hallmark gene sets in the MSigDB database. CONCLUSIONS: In this study, we used machine learning algorithms to screen out 17 genes related to the survival risk of HCC patients, and trained a DNN model based on them to predict the survival risk of HCC patients. The genes that make up the model are all key genes that affect the formation and development of cancer. Show more
Keywords: Hepatocellular carcinoma, TCGA, machine learning, deep neural network, prediction model, survival
DOI: 10.3233/CBM-220147
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 305-320, 2022
Authors: Zhang, Yan | Zhang, Qianqian | Xu, Lin | Wang, Weiwen | Xiao, Hua | Luo, Bing
Article Type: Research Article
Abstract: BACKGROUND AND OBJECTIVE: EBV-associated gastric cancer (EBVaGC) is a distinct subtype of GC, and EBV plays an important role in tumor progress. The standard method to identify EBV-positive tumor is determined by in situ hybridization for EBV-encoded EBERs in tumor tissues. The present study aims to detect the serological expression of EBV-related antibodies and ET-1 axis to provide a noninvasive method for diagnosis of EBVaGC. METHODS: The content of EBV-related antibodies and ET-1 axis in preoperative peripheral blood of GC was performed by Chemiluminescence and ELISA assay. The EBV DNA copy number was measured by …qRT-PCR. RESULTS: The results showed that the levels of anti-EBV early antigen (EA) IgG, viral capsid antigen (VCA) IgA, nuclear antigen (NA) IgG, and EBV DNA copy number were significantly higher in EBVaGC. The ET-1 axis level was much lower in EBVaGC than EBVnGC. CONCLUSIONS: The combined detection of specific anti-EBV antibodies and ET-1 axis might provide new molecular markers for the identification of EBVaGC. Show more
Keywords: EBV-related antibodies, ET-1, ETAR, ETBR, DNA copy number
DOI: 10.3233/CBM-220001
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 321-329, 2022
Authors: Tu, Junhao | Wang, Jun | Tang, Binxiang | Zhang, Zhiqiang | Han, Mei | Li, Mengyue | Yu, Jieqing | Shen, Li | Zhang, Meiping | Ye, Jing
Article Type: Research Article
Abstract: BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a lethal malignancy with poor prognosis. Treatment outcomes of SNMM are poor. Novel prognostic or progression markers are needed to help adjust therapy. METHODS: RNA-seq was used to analyze the mRNA expression of tumor tissues and normal nasal mucosa from primary SNMM patients (n = 3). Real-time fluorescent quantitative PCR (qRT-PCR) was used to validate the results of RNA-seq (n = 3), while protein expression was analyzed by immunohistochemistry (IHC, n = 31) and western …blotting (n = 3). Retrospective studies were designed to determine the clinical parameters and the total survival rate, and correlation between the protein expression levels of the most significant key genes and prognosis was analyzed. RESULTS: In total, 668 genes were upregulated and 869 genes were downregulated in SNMM (fold change ⩾ 2, adjusted p value < 0.01). Both mRNA and protein expression levels of the key genes in SNMM tumor tissues were higher than those in the normal control nasal mucosal tissues. The expression rates of TYRP1, ABCB5, and MMP17 in 31 primary SNMM cases were 90.32%, 80.65%, and 64.52%, respectively. In addition, age, typical symptoms, and AJCC stage were related to overall survival rate of patients with SNMM (p < 0.05). Furthermore, the expression of ABCB5 was age-related (p = 0.002). Compared with individuals with negative ABCB5 expression, those with positive expression exhibited significantly poor overall survival (p = 0.02). CONCLUSION: The expression levels of TYRP1, ABCB5, and MMP17 were significantly upregulated in SNMM tissues, and the expression of ABCB5 was related to poor prognosis in SNMM. Thus, ABCB5 may serve as a progression marker and can predict unfavorable prognosis in patients with SNMM. Show more
Keywords: RNA-seq, sinonasal mucosal melanoma, mucosal melanoma, prognosis, TYRP1, ABCB5, MMP17
DOI: 10.3233/CBM-220093
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 331-342, 2022
Article Type: Retraction
DOI: 10.3233/CBM-229005
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 343-343, 2022
Article Type: Retraction
DOI: 10.3233/CBM-229006
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 345-345, 2022
Article Type: Retraction
DOI: 10.3233/CBM-229007
Citation: Cancer Biomarkers, vol. 35, no. 3, pp. 347-347, 2022
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