HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer

HIWI is a member of PIWI gene family and its expression is found in various tumors, indicating that it may play a pivotal role in tumor development. This study was designated to examine HIWI protein expression profile in several cancer cell lines and its prognostic value for patients with colorectal cancer.

Totally 270 patients who underwent surgical resection of primary colorectal cancer between January 1999 and December 2002 with a median follow-up time of 33 months were registered in the study. Formalin-fixed and paraffin-embedded specimens from these patients and 236 matched adjacent non-cancerous normal colorectal tissues were collected. Anti-HIWI monoclonal antibodies were generated and used for evaluating HIWI protein expression. χ(2) tests were conducted to determine the association between HIWI expression and the other variables. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed by using the Cox regression model.

By generating antibodies specific for HIWI, we examined HIWI protein expression in several cancer cell lines and demonstrated positive expression of HIWI in 69 out of 270 (25.6%) colorectal cancer tissues; 15 of 236 (6.4%) matched adjacent non-cancerous tissues were also positive for HIWI. Patients with positive HIWI expression in adjacent non-cancerous tissue had statistically lower overall survival (OS) and disease free survival (DFS) compared with negative patients (OS: 10.4% vs. 55.5%, P = 0.009; DFS: 10.4% vs. 55.1%, P = 0.015). For early stage group (stages I and II), patients with positive HIWI expression had significantly lower OS and DFS (OS: 57.4% vs. 79.5%, P = 0.014; DFS: 56.7% vs. 80.5%, P = 0.010). In lymph node negative group, patients with positive HIWI expression had statistically lower OS and DFS (OS: 53.0% vs. 73.5%, P = 0.037; DFS: 52.2% vs. 74.6%, P = 0.025). Multivariate analysis revealed that HIWI over-expression was a significant prognostic factor for OS (95%CI: 1.132 - 2.479, P = 0.010).

HIWI could be a potential prognostic biomarker for the patients with colorectal cancer, especially for those at early stages or without lymph node metastasis.