High WNT6 expression indicates unfavorable survival outcome for patients with colorectal liver metastasis after liver resection

Objective: As a member of the Wnt family, WNT6 contributes to tumorigenesis and the development of various types of cancer. However, the expression status of WNT6 in colorectal liver metastasis (CRLM) and its prognostic value remain to be elucidated. In this study, we evaluated the association of WNT6 expression with survival outcomes in CRLM patients undergoing liver resection. Methods: The medical records of 106 consecutive CRLM patients undergoing curative tumor resection between October 1996 and December 2011 were retrospectively selected. WNT6 expression was detected using immunohistochemistry (IHC) analyses on paraffin-embedded specimens. The IHC score was determined according to the percentage and intensity of positively stained cells. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test, and independent prognostic factors were determined by Cox regression modeling. Results: We found that WNT6 was commonly expressed in 93.4% (99/106) of colorectal cancer tissues. The median IHC score of WNT6 expression was significantly lower in patients receiving preoperative chemotherapy than those without preoperative chemotherapy (1.33 vs. 2.33, P = 0.033). Survival analysis indicated that patients with high WNT6 expression had poorer 5-year OS than those with low WNT6 expression (31.0% vs. 62.2%, P = 0.012). The 5-year OS rate was significantly lower in the high WNT6 group than in the low WNT6 group (36.8% vs. 79.9%, P = 0.013) in low-risk patients but was comparable among the high-risk patients (22.7% vs. 34.7%, P = 0.433). Multivariate analysis indicated that high WNT6 expression was independently associated with poor OS (hazard ratio [HR]: 2.089; 95% confidence interval [CI]: 1.231-3.545; P = 0.006). Conclusions: High expression of WNT6 was associated with unfavorable oncologic prognosis in patients with CRLM undergoing liver resection. Detection of WNT6 expression may be valuable for guiding postoperative treatment.