Dataset Information

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

ABSTRACT: Background:The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods:Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results:COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference?=?0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions:Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

SUBMITTER: Peng W

PROVIDER: S-EPMC7427770 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

Peng Wei W Li Jian-Di JD Zeng Jing-Jing JJ Zou Xiao-Ping XP Tang Deng D Tang Wei W Rong Min-Hua MH Li Ying Y Dai Wen-Bin WB Tang Zhong-Qing ZQ Feng Zhen-Bo ZB Chen Gang G

Cancer cell international 20200814

<h4>Background</h4>The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown.<h4>Methods</h4>Gene microarrays and mRNA sequencing data were downloaded and integrated ...[more]

PMID: 32818022

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Project description:BackgroundDesmoglein-2 (DSG2), a desmosomal adhesion molecule, is found to be closely related to tumorigenesis in recent years. However, the clinical value of DSG2 in lung adenocarcinoma remains unclear.MethodsReal-time reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression of DSG2 in 40 paired lung adenocarcinoma tissues and corresponding non-cancerous tissues. Data from The Cancer Genome Atlas (TCGA) and Oncomine datasets were also downloaded and analyzed. The correlation between DSG2 and clinicopathological features was investigated. The expression of DSG2 protein by immunohistochemical was also detected from tissue microarray and the Human Protein Atlas database. Integrated meta-analysis combining the three sources (qRT-PCR data, TCGA data and Oncomine datasets) was performed to evaluate the clinical value of DSG2. Univariate and multivariate Cox regression analyses were used to explore the prognostic value of DSG2. Then, co-expressed genes were calculated by Pearson correlation analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to investigate the underlying molecular mechanism. The expression level in lung adenocarcinoma and prognostic significance of the top ten co-expressed genes were searched from Gene Expression Profiling Interactive Analysis (GEPIA) online database.ResultsDSG2 was highly expressed in lung adenocarcinoma tissues based on qRT-PCR, TCGA and Oncomine datasets. The protein expression of DSG2 was also higher in lung adenocarcinoma. According to qRT-PCR and TCGA, high DSG2 expression was positively associated with tumor size (p = 0.027, p = 0.001), lymph node metastasis (p = 0.014, p < 0.001) and TNM stage (p = 0.023, p < 0.001). The combined standard mean difference values of DSG2 expression based on the three sources were 1.30 (95% confidence interval (CI): 1.08-1.52) using random effect model. The sensitivity and specificity were 0.73 (95% CI [0.69-0.76]) and 0.96 (95% CI [0.89-0.98]). The area under the curve based on summarized receiver operating characteristic (SROC) curve was 0.79 (95% CI [0.75-0.82]). Survival analysis revealed that high DSG2 expression was associated with a short overall survival (hazard ratio [HR] = 1.638; 95% CI [1.214-2.209], p = 0.001) and poor progression-free survival (HR = 1.475; 95% CI [1.102-1.974], p < 0.001). A total of 215 co-expressed genes were identified. According to GO and KEGG analyses, these co-expressed genes may be involved in "cell division", "cytosol", "ATP binding" and "cell cycle". Based on GEPIA database, seven of the top ten co-expressed genes were highly expressed in lung adenocarcinoma (DSC2, SLC2A1, ARNTL2, ERO1L, ECT2, ANLN and LAMC2). High expression of these genes had shorter overall survival.ConclusionsThe expression of DSG2 is related to the tumor size, lymph node metastasis and TNM stage. Also, DSG2 predicts poor prognosis in lung adenocarcinoma.

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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

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