Patra Ritwik, Das Nabarun Chandra, Mukherjee Suprabhat
Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol, India.
Front Genet. 2021 Feb 1;12:608313. doi: 10.3389/fgene.2021.608313. eCollection 2021.
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.
结直肠癌是人类最常见的癌症之一，在癌症相关死亡中位列第二。用作预后生物标志物的基因在癌症检测中起着至关重要的作用，并可能指导合适治疗策略的制定。XI型胶原蛋白α1（COL11A1）是一种微小纤维状胶原蛋白，在调节肠道和结肠细胞的分裂、分化、增殖、迁移、生长和凋亡中发挥着重要作用。本研究旨在运用先进的生物信息学方法，评估COL11A1基因在人类结直肠癌进展过程中各项参数的意义。通过访问ONCOMINE、UALCAN和GEPIA等各种数据库和服务器，分析COL11A1基因的差异表达及其对转化受试者生存的相对影响。此外，使用COSMIC、cBioPortal、GeneMANIA和NetworkAnalyst研究了COL11A1基因的肿瘤基因组学、与该基因相关的突变以及该基因在肿瘤发生背景下的相互作用伙伴。我们的实验数据表明，在各种临床病理参数中，COL11A1基因在转化组织中过度表达，这降低了总体生存和疾病特异性生存情况下的生存概率。突变研究表明，它可在各种信号通路中引发扰动，即RTK-RAS-PI3K、Wnt、TGF-β和TP53通路，从而影响癌症发展。此外，还观察到THBS2、COL10A1、COL5A2和COL1A2基因之间存在正相关和关联，这很可能导致致癌作用的上调。总之，这项全面的研究表明COL11A1基因是结直肠癌病因学中的一个重要因素，因此在不久的将来，该基因可被视为制定结直肠癌诊断和治疗策略的预后生物标志物。
