The Prognostic Biomarkers and Immunotherapeutic Targets of Septin in Colon Cancer

Abstract

BackgroundColon cancer has the third highest incidence and second highest death rate in the world. Colon cancer poses a huge burden to patients and society in China. More accurate and convenient early diagnosis of colon cancer is a challenge to solve this disease. Some studies have revealed the involvement of Septin family members in colon cancer, but the role of most Septin remains unclear. MethodsGEPIA, UALCAN, The Human Protein ATLAS database, The Human Disease Methylation Database, MethSurv, SurvivalMeth, cBioPortal, STRING, GeneMANIA, DAVID, Metascape, PASTAA, LinkedOmics, and TIMER were used in our study. ResultsWe found that the transcription level of SEPT1/4/5/6/7/10/11 was significantly decreased in colon cancer tissues. The expression level of SEPT2/5/6/7/8/9/10/11 protein was medium to high in colon cancer tissues, while the relative expression level of SEPT2 and SEPT9 was the highest in colon cancer tissues. SEPT7 expression was significantly correlated with pathological stage. For colon cancer patients, high SEPT2/9/10/11 expression was associated with longer OS, and only low SEPT4 expression was obviously associated with longer DSF. Moreover, the methylation level of SEPT2/5/7/8/9/11 was increased in colon cancer tissues, while that of SEPT3/4/6/10 was decreased. SEPT9/10/11 methylation levels were also found to decrease with the progression of colon cancer. 2 CpG SEPT1 2 CpG SEPT3, 5 CpG SEPT4, 3 CpG SEPT5, 8 CpG SEPT6, 3 CpG SEPT7, 5 CpG SEPT8, 20 CpG SEPT9, SEPT10 3 CpG 7 CpG SEPT11 was significantly associated with the prognosis of colon cancer patients. We found that SEPT7 had the lowest level of DNA methylation, while SEPT2 had the highest. For possible mechanisms, we performed interaction analysis, functional enrichment analysis in colon cancer, and identified the transcription factor targets and miRNA targets of septin in colon cancer. We also found a significant association between Septin and immune cell invasion. The results showed that SEPT4 and SEPT5 were significantly associated with clinical outcomes of colon cancer patients.ConclusionsSeptin could be used as a clinical prognostic biomarkers and immunotherapeutic targets for colon cancer.