Decreased expression of PinX1 protein predicts poor prognosis of colorectal cancer patients receiving 5-FU adjuvant chemotherapy.

Abstract

Previous studies suggest that Pin2/TRF1 interacting protein X1 (PinX1) is an intrinsic telomerase inhibitor and a putative tumor suppressor gene in human cancers. The aims of this study were to investigate PinX1 expression status in colorectal cancer (CRC) specimens and to clarify its clinical significance. A total of 83 CRC patients treated with radical resection and 5-fluorouracil (5-FU) based adjuvant chemotherapy were enrolled in this study. Immunohistochemistry was used to detect PinX1 and human telomerase reverse transcriptase (hTERT) protein expression in paired tumor and adjacent normal tissues. Results showed that PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, the rate of PinX1 protein low/negative expression in CRC and normal tissues was 43.4% (36/83) and 9.6% (8/83), respectively (P<0.001), while hTERT protein expression was upregulated in CRC and negative correlated with PinX1 expression. Although no correlations with clinicopathological features, PinX1 downregulation was significantly associated with adverse 5-year overall survival (OS) and disease-free survival (DFS). Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting OS and DFS for CRC patients, apart from lymph metastasis. In conclusion, PinX1 protein expression is decreased in CRC, which may be a new promising tumor marker for CRC prognosis and 5-FU chemosensitivity.