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

PeerJ. 2019 Oct 4:7:e7705. doi: 10.7717/peerj.7705. eCollection 2019.


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.

Keywords: Collagen; ESCC; GEO; Gene expression; Overall survival; TCGA.

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (Nos. 81602625), the Natural Science Foundation of Guangdong Province (2016A030310096, 2018A030313122), the Science and Technology Planning Project of Guangdong Province (2017A010105013), the Pearl River S&T Nova Program of Guangzhou (201710010011), and the Shenzhen Science and Technology Project (JCYJ20170302145059926, JCYJ20180305163658916, JCYJ20180228175059744). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.