Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer.

BACKGROUND

Transmembrane serine protease 2 (TMPRSS2) mediates the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The relevant research indicates the intestine to be a target of SARS-CoV-2 infection, and thus we aimed to investigate the correlation between expression and the prognosis, molecular features, and immunotherapy response in patients with colorectal cancer (CRC).

METHODS

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study and a total of 1,385 patients were identified. The CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in the tumor microenvironment (TME). The correlation between expression and immunotherapy response rate was assessed in another 2 independent cohorts.

RESULTS

expression was significantly downregulated in cancer tissue compared to the adjacent normal tissue, and patients with CRC with lower expression showed notably poorer prognosis. Functional enrichment analysis found that low expression was significantly associated with cancer metastasis-related pathways. Further analysis based on the miRWalk tool and JASPAR database identified a list of microRNAs (miRNAs) and transcriptional factors targeting . Distinct differences in immune cell infiltration and tumor purity reflected by estimate and mutant-allele tumor heterogeneity score were observed between patients with low and high expression levels. Interestingly, patients with a low expression level showed a higher response rate to immunotherapy.

CONCLUSIONS

CRC cells may be more resistant to SARS-CoV-2 infection due to the decreased expression of , which could be a newly identified biomarker for prognosis and immunotherapy response prediction in patients with CRC.