Data mining-based study of collagen type III alpha 1 (COL3A1) prognostic value and immune exploration in pan-cancer

The extracellular matrix (ECM) shows an essential effect during the occurrence and procession of human cancers. Type III collagen is a crucial component of ECM. Collagen Type III Alpha 1(COL3A1) is aberrantly expressed in a variety of cancers. Nevertheless, the role of COL3A1 in pan-cancer stays unidentified. In this study, we explored public databases, including Cancer Genome Atlas (TCGA), GTEx, GEPIA, cBioPortal, Oncommine, TIMER and GENEMANIA databases to identify the differential expression of COL3A1 in human cancer tissues and normal samples, followed by its prognostic value for patient survival. In addition, we explore the association between COL3A1 expression and immune infiltration. Further, we used the GeneMANIA database and Gene Set Enrichment Analysis (GSEA) to investigate Protein–Protein Interaction (PPI) and gene functional enrichment. Results show that COL3A1 expressed higher in tumor samples than in normal samples. Upregulation of COL3A1 is associated with a worse prognosis and a more advanced cancer stage. COL3A1 expression shows significant positive correlations with tumor-infiltrating immune cells (TIICs), including neutrophils, macrophages, CD8 + T cells, CD4 + T cells, dendritic cells, and B cells. Markers of TIICs demonstrated distinct patterns of COL3A1-related immune infiltration. COL3A1 expression was associated with ECM receptor interaction, regulation of actin cytoskeleton and focal adhesion pathways via GSEA analysis. In conclusion, COL3A1 may be a molecular biomarker for prognosis and immune infiltration in pan-cancer. It might act as a potential target for a new insight of human cancers management.

细胞外基质（extracellular matrix, ECM）在人类癌症的发生与进展过程中发挥不可或缺的作用。III型胶原（Type III collagen）是细胞外基质的关键组成成分，而III型胶原α1链（Collagen Type III Alpha 1, COL3A1）在多种癌症中存在异常表达。然而，COL3A1在泛癌中的作用仍未明确。本研究通过检索癌症基因组图谱（Cancer Genome Atlas, TCGA）、GTEx、GEPIA、cBioPortal、Oncommine、TIMER及GENEMANIA等公共数据库，首先分析COL3A1在人类癌组织与正常样本中的差异表达情况，随后探究其对患者生存的预后价值。此外，本研究还探究了COL3A1表达与免疫浸润之间的关联。进一步，本研究借助GeneMANIA数据库及基因集富集分析（Gene Set Enrichment Analysis, GSEA），对蛋白质-蛋白质相互作用（Protein–Protein Interaction, PPI）及基因功能富集情况进行了分析。研究结果显示，COL3A1在肿瘤样本中的表达水平显著高于正常样本。COL3A1的高表达与不良预后及更高的癌症分期密切相关。COL3A1表达与肿瘤浸润免疫细胞（tumor-infiltrating immune cells, TIICs）包括中性粒细胞、巨噬细胞、CD8+T细胞、CD4+T细胞、树突状细胞及B细胞均呈显著正相关。肿瘤浸润免疫细胞的标志物呈现出与COL3A1相关的独特免疫浸润模式。通过基因集富集分析（GSEA）可知，COL3A1的表达与细胞外基质受体相互作用、肌动蛋白细胞骨架调控及黏着斑通路密切相关。综上，COL3A1有望成为泛癌中预后及免疫浸润相关的分子生物标志物，或可为人类癌症诊疗的新策略提供潜在靶点。