Identification and validation of PSAT1 as a potential prognostic factor for predicting clinical outcomes in patients with colorectal carcinoma

摘要

The aim of the present study was to explore the existence of known or candidate drug-target genes that are upregulated in colorectal cancer (CRC) and may serve as novel prognostic factors or therapeutic targets for this type of malignancy. An in silico analysis was conducted using the Oncomine tool to compare the expression levels of a list of drug-target genes between cancerous and normal tissues in 6 independent CRC cohorts retrieved from the Oncomine database. Phosphoserine aminotransferase 1 (PSAT1) was identified as the top-ranked upregulated gene in CRC tumors, and was highly expressed in patients with chemo-resistant disease. Subsequently, the expression of PSAT1 was further experimentally validated using immunohistochemistry in an independent cohort of CRC specimens. The immunohistochemistry results demonstrated that PSAT1 was overexpressed in the CRC tissues compared with the normal colorectal tissues, which was consistent with the previous in silico analysis. Furthermore, PSAT1 overexpression was associated with response to irinotecan, 5-fluorouracil and leucovorin chemotherapy, and with shorter survival time, and retained significance as an independent prognostic factor for CRC when subjected to the multivariate analysis with a Cox's proportional hazards model. Therefore, the present results implicate PSAT1 as a potential prognostic biomarker and a promising therapeutic target for CRC. Targeted PSAT1 inhibition in the treatment of CRC warrants further investigation.