Upregulation of The Transmembrane Protease Serine 3 (TMPRSS3) mRNA Level In Radioresistant Colorectal Cancer Tissues

Abstract BackgroundPrevious studies have shown that transmembrane protease serine 3 (TMPRSS3) is abnormally expressed in various tumours and its expression is closely related to tumorigenesis and progression [1-3]. However, there have been no reports regarding the role of TMPRSS3 in colorectal cancer (CRC). The aim of the current study was to comprehensively explore the clinical value of TMPRSS3 on the radioresistance of CRC.MethodsIn this study, we evaluated the expression level of TMPRSS3 in radioresistant CRC tissues as well as CRC tissues by analysing public data sets from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress, and GTEx databases, as well as explored the relationship between TMPRSS3 and lymph node metastasis, distant metastasis, and prognosis. In addition, we investigated the biological function of TMPRSS3 by gene ontology (GO) and analysis of the Kyoto Encyclopaedia of Genes and Genomes (KEGG). Finally, we created a protein-protein interaction (PPI) network to identify hub genes that may function in concert with TMMPRSS3.ResultsEight radiation-processed CRC tissue data sets and 26 CRC mRNA data sets were obtained. The pooled analysis revealed that TMPRSS3 was significantly highly expressed in CRC radioresistant tissues—SMD = 0.38 (95% CI: 0.14~0.63; p-value < 0.05). In addition, TMPRSS3 is also as highly expressed in CRC tissues—SMD = 1.55 (95% CI: 1.20~1.90; p-value < 0.05). Subsequently, we explored the relationship between TMPRSS3 and both metastasis and prognosis. The results revealed no relationship between TMPRSS3 and lymph node metastasis and distant metastasis (p-value > 0.05). Furthermore, pooled analysis of HR revealed that TMPRSS3 could be used as a risk factor for DFS—SMD = 1.28 (95% CI: 1.03~1.60; p-value < 0.05). Finally, we obtained 429 co-expressed genes for bioinformatics analysis and selected a total of four hub genes: MSLN, MFI2, CKAP4, and PXN. The results revealed that these genes cooperate with TMPRSS3 to participate in biological processes, such as CRC development, metastasis, and radioresistance by affecting autophagy, cell-cell adhesion, and extracellular matrix breakdown.ConclusionThis study reveals that TMPRSS3 has potential as a new biomarker and radioresistant therapeutic target for CRC and also has a few implications for the prognosis of CRC patients. However, this conclusion must be further experimentally verified.