Objective To investigate the expression of collagen type Ⅻ α1 chain (COL12A1) in tissues of colon cancer and its relationships with clinicopathological characteristics and prognosis of patients with colon cancer.
Methods The difference of COL12A1 expression level between colon cancer tissues and adjacent tissues was analyzed by The Cancer Genome Atlas (TCGA) database, and the relationships of COL12A1 with tumor microenvironment and immune invasion were analyzed by the TIMER database. Gene Set Enrichment Analysis (GSEA) was used to explore the related signal pathways of COL12A1 playing its biological functions in colon cancer. Immunohistochemistry (IHC) was used to evaluate the expression of COL12A1 in 47 cases of colon cancer and normal colon mucosa adjacent to the cancer, and its relationship with the clinicopathological characteristics of colon cancer patients was analyzed as well; the Western blot (WB) was used to detect the expression level of COL12A1 in colon cancer cell lines and normal colon mucosa cell lines. GEPIA and PrognoScan online analysis websites were used to analyze the relationship between the expression of COL12A1 and the prognosis in patients with colon cancer.
Results The analysis of colon cancer dataset of TCGA database showed that the expression of COL12A1 in colon cancer tissues was significantly higher than that in normal tissues (P < 0.001); the IHC result showed that the expression of COL12A1 in colon cancer tissues was significantly higher than that in normal adjacent tissues (P < 0.000 1). In colon cancer tissues, the expression level of COL12A1 was related to nerve or vascular invasion (P=0.029), lymph node metastasis (P=0.003), and TNM staging (P=0.001). Online database analysis showed that patients with high expression of COL12A1 had a shorter disease-free survival. The expression of COL12A1 was positively correlated with CD8+ T cells, B cells, CD4+ T cells, macrophages, eosinophils, neutrophils and dendritic cells in colon cancer microenvironment (P < 0.001). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that COL12A1 expression involved in signal pathways such as cell adhesion, chemical synaptic transmission, cytokine receptor interaction, cell matrix receptor interaction and autophagy regulation.
Conclusion COL12A1 is highly expressed in colon cancer cell lines and tissues, and is positively related to the poor prognosis of patients. The expression of COL12A1 is positively correlated with the immune cell infiltration of colon cancer microenvironment, and COL12A1 may be a new prognostic marker for colon cancer and a potential target for immunotherapy.
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