AUTHOR=Liu Yi , Xue Jinmin , Zhong Maoxi , Wang Zhi , Li Jie , Zhu Yuxi 

TITLE=Prognostic Prediction, Immune Microenvironment, and Drug Resistance Value of Collagen Type I Alpha 1 Chain: From Gastrointestinal Cancers to Pan-Cancer Analysis

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.692120

DOI=10.3389/fmolb.2021.692120

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> Gastrointestinal cancers patients might experience multiple primary tumors in the digestive tract. Therefore, identifying potential biomarkers can help us better understand the underlying mechanism. From the GEO database, four profiles of gastrointestinal cancers were gathered for the screening process, and six hub genes were found by bioinformatics analysis. <italic>Collagen type I alpha 1 chain</italic> (<italic>COL1A1</italic>), one of the hub genes, is a component of the extracellular matrix and is critical for tumor microenvironment. However, the expression level, signaling pathway, prognostic prediction, and immunological value of <italic>COL1A1</italic> in different cancers remain unclear.</p><p><bold>Methods:</bold> We comprehensively analyzed gene expression and genetic alteration patterns of <italic>COL1A1</italic> among 33 types of malignancies from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects. Besides, we explored the correlation of <italic>COL1A1</italic> with cancer prognosis, immune infiltrates, PD-L1, tumor mutational burden (TMB)/microsatellite instability status (MSI), and the pathway and drug sensitivity of co-expressed genes.</p><p><bold>Results:</bold> The results showed that <italic>COL1A1</italic> was highly expressed and associated with poor prognosis in the majority of cancers. The most common alteration type of <italic>COL1A1</italic> was missense mutation, and <italic>COL1A1</italic> was associated with poor prognosis in KIRP, LGG, MESO, SKCM, and STAD. For the immunologic significance, <italic>COL1A1</italic> expression was closely related to high TMB in THYM, LAML, ACC, KICH, PRAD, and LGG, and high MSI in TGCT, MESO, PRAD, COAD, SARC, and CESC. In addition, <italic>COL1A1</italic> was positively correlated with the abundance of CAFs, macrophages, and tumor-infiltrating lymphocytes. However, it was negatively correlated with CD8<sup>+</sup> T cells mainly in CESC, HNSC-HPV+, and SKCM. Besides, as a component of the extracellular matrix, <italic>COL1A1</italic> was involved in the activation of epithelial-mesenchymal transition (EMT), and high expression of <italic>HTRA1</italic> was resistant to multiple drugs.</p><p><bold>Conclusion:</bold><italic>COL1A1</italic> can serve as a prognostic and immunological biomarker in different cancers.</p>