The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Abstract

Background Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers. Methods Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC. Results A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc. Conclusion Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.

MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation

“…However, levels of COL11A1, which encodes collagen XI alpha 1 chain, are significantly increased when cSCC advances from moderate to poor differentiation (1132.56±882.7 vs. 197.6±267.2; p = 0.014). Similar findings were also reported in the study of Li et al in esophageal SCC patients; however, we did not find any changes in other collagens [ 54 ]. Increased collagen XI expression is associated with fibroblasts in various cancers, including lung and breast, and is considered as a potential biomarker for cancer invasiveness [ 55 – 57 ].…”

Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix

“…Over the past few decades, the notion that tumors secrete MMPs to degrade type I collagen in ECM has been very well accepted [51]. Recent studies, however, have described how cancer cells also produce their own type I collagen molecules, nevertheless presenting a different molecular weight from that of stromal cells, particularly in the case of EC [52,53]. Cancer-derived type I collagen molecules may affect tumor microenvironment and, although the precise mechanisms need to be explored, it is already known that tumor type I collagen facilitates cancer cell adhesion by modulating ECM to contribute to tumor clone formation [52,53].…”

“…Recent studies, however, have described how cancer cells also produce their own type I collagen molecules, nevertheless presenting a different molecular weight from that of stromal cells, particularly in the case of EC [52,53]. Cancer-derived type I collagen molecules may affect tumor microenvironment and, although the precise mechanisms need to be explored, it is already known that tumor type I collagen facilitates cancer cell adhesion by modulating ECM to contribute to tumor clone formation [52,53]. Thus, one could suggest that cancer-derived type I collagen represents a promising target to improve cancer diagnosis and treatment, pointing out the need to further elucidate their function, particularly in EC.…”

Anlotinib Combined With Chemoradiotherapy Exhibits Significant Therapeutic Efficacy in Esophageal Squamous Cell Carcinoma

“…Targeted drugs directed against molecules involved in the pathogenesis and progression of cancer have achieved successful clinical outcomes in other cancers. Genomic profiling using next-generation sequencing (NGS) has been conducted and has identified some candidate therapeutic targets for ESCC ( 19 – 21 ). However, clinical studies have shown that effective single-target drugs for ESCC are still lacking because of the complexity of signaling networks.…”