Abstract

Colorectal cancer is one of the most common cancers of humans and the second highest in cancer-related death. Genes used as prognostic biomarkers play an imperative role in cancer detection and may direct the development of appropriate therapeutic strategies. Collagen type XI alpha 1 (COL11A1) is a minor fibrillary collagen that has an essential role in the regulation of cell division, differentiation, proliferation, migration, growth, and apoptosis of intestinal and colon cells. The present study seeks to evaluate the significance of the COL11A1 gene in the progression of colorectal cancer in humans across the various parameters using advanced bioinformatics approaches. The application of various databases and servers like ONCOMINE, UALCAN, and GEPIA were accessed for analyzing the differential expression of the COLL11A1 gene and its relative influence over the survival of the transformed subjects. In addition, oncogenomics of COL11A1 gene, mutations associated with this gene and interacting partners of the gene in the context of oncogenesis were studied using COSMIC, cBioPortal, GeneMANIA, and NetworkAnalyst. Our experimental data indicate that the COL11A1 gene is overexpressed in the transformed tissues across the various clinicopathological parameters reduces the probability of survival in both overall and disease-specific survival cases. Mutational studies imply that it can induce perturbations in various signaling pathways viz. RTK-RAS-PI3K, Wnt, TGF-β, and TP53 pathways influencing cancer development. Also, a positive association and correlation amongst the THBS2, COL10A1, COL5A2, and COL1A2 genes were observed, which most likely to contribute to the upregulation of carcinogenesis. Conclusively, this comprehensive study indicates the COL11A1 gene to be a significant contributor in the etiology of colorectal cancer, henceforth this gene can be considered as a prognostic biomarker for the conception of diagnostic and therapeutic strategies against colorectal cancer in the near future.

Highlights

  • Colorectal cancer is considered as the third most common cancer in the world and is in the second position for cancer-related death of humans worldwide (Siegel et al, 2017)

  • Considering the background, the objective of the present study is to collectively examine the differential expression, survival, co-expression, correlation, mutations, and protein-protein interaction network that result in the alteration of various pathways related to the COL11A1 gene playing a key role in the transformation of human colon tissue to colorectal cancer using an integrated bioinformatics approach

  • The TIMER analysis reveals that the comparison of the COL11A1 gene across various cancer types including colon cancer and displays that it is significantly upregulated for colon adenocarcinoma

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Summary

Introduction

Colorectal cancer is considered as the third most common cancer in the world and is in the second position for cancer-related death of humans worldwide (Siegel et al, 2017) It is a multi-stage process that gradually develops with the initiation of transformation in normal colon tissue to an adenomatous intermediate by the consequences of mutation, epigenetic changes, DNA damage, uncontrolled growth with gene and chromosomal instability as well as defects leading to invasive adenocarcinoma (Zhang et al, 2011). Several experiments on the transformed cells display significant alteration in a number of cellular signaling pathways, including Wnt, TGF-β, RTK-RAS-PI3K, and TP53 signaling pathways which might be the crucial contributors of the neoplastic transformation (Li et al, 2015; Koveitypour et al, 2019) All these various studies imply that the COL11A1 gene is crucial in the progression of various cancer, the actual significance across the various clinicopathological factors including cancer-stage, nodal metastasis status, age group, etc., have not been documented comprehensively till date

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