Critical evaluation of Cbx7 downregulation in primary colon carcinomas and its clinical significance in Chinese patients.

ABSTRACT

BACKGROUND: CBX7 is a Polycomb group protein that shows variable expression changes in various cancers that are often contradictive. A mouse knockout experiment has validated the tumor suppressor role in carcinogenesis. The purpose of this study is to verify the tumor suppressor role of Cbx7 in human colon carcinomas (CC). METHODS: Frozen CC and the surgical margin (SM) tissue samples from patients (n = 97) were obtained from the Peking University Cancer Hospital. All patients had follow-up data for at least three years. The level of Cbx7 mRNA and protein was determined by quantitative RT-PCR, immunohistochemistry and Western blot, respectively. The association between Cbx7 mRNA level and clinicopathological characteristics of CC patients was then statistically analyzed. RESULTS: CBX7 expression changes detected through immunohistochemistry and Western blot in 10 pairs of representative CC samples significantly correlated with their corresponding mRNA levels when Alu, but not GAPDH, was used as the endogenous reference control in quantitative RT-PCR. The Alu-normalized Cbx7 mRNA levels were significantly increased in SM tissues when compared with CC tissues or colon biopsies taken from non-cancer patients (Student's t-test, P < 0.036 or 0.007). Furthermore, decreased levels of Cbx7 mRNA positively correlated with lymph metastasis (P = 0.029). Overall survival (OS) of CC patients classified as Cbx7 expression-low was considerably shorter than those classified as Cbx7 expression-high (Hazard ratio = 2.97, 95% CI [1.68 ~ 5.25]; P <0.001). Multiple variant analyses showed that the Cbx7 expression-low was an independent predictor of short OS (Hazard ratio = 3.16, 95% CI [1.58-6.30]; P < 0.001). CONCLUSION: Cbx7 is downregulated in CCs, and Cbx7 expression-low tumors correlated with lymph metastasis and poor overall survival of CC patients.