Background: SCARA5 has been demonstrated to be a tumor suppressor gene, with its expression downregulated in many cancer types. However, only few studies have investigated its role in colorectal cancer (CRC). The current study evaluated SCARA5 expression levels in CRC and its potential value as a diagnostic biomarker for CRC.
Methods: Data were downloaded from the TCGA, GEO, and Oncomine databases to evaluate SCARA5 mRNA expression levels in CRC. The prognosis value of SCARA5 was assessed using the online tool Cutoff Finder via the Kaplan-Meier plotter (n = 484). Immunohistochemistry was performed to analyze and compare the SCARA5 protein expression levels in CRC and normal tissues from 67 CRC clinical specimens. Relevant CRC CNV data were downloaded from TCGA and cBioPortal for Cancer Genomics databases to assess the associated genetic alterations. GSEA was used to explore the underlying molecular mechanisms of SCARA5. The correlation between SCARA5 mRNA levels and cell cycle-associated genes was explored using GEPIA database.
Results: SCARA5 mRNA levels were found to be downregulated in CRC tissues compared with normal tissues. Survival analysis showed that low SCARA5 expression was associated with poor prognosis. These results were validated in clinical specimens, wherein the SCARA5 protein levels were significantly downregulated in CRC tissues compared with paracarcinoma tissues. Deep deletion was the most common genetic alteration and was consistent with the downregulated SCARA5 expression in CRC tissues. GSEA indicated that the gene sets of CELL CYCLE, G2M CHECKPOINT, and E2F TARGETS were negatively related to SCARA5 mRNA expression. GEPIA indicated that the mRNA expression of some cell cycle-associated genes was negatively correlated with that of SCARA5 in CRC.
Conclusions: Thus, SCARA5 may act as a human cancer suppressor gene in CRC, and its expression level may be a reliable adjuvant parameter to diagnose CRC and predict tumor metastasis and prognosis.