Wnt通路新调控因子R-spondin家族在结直肠癌中的表达及其临床意义

目的：探讨结直肠癌及癌旁组织中R-spondin家族的表达水平及其与患者临床病理分期之间的关系。 方法：收集中南大学湘雅医院2014年1月至2014年8月行根治性手术治疗后的64例结直肠癌新鲜组织及配对的癌旁组织 标本，利用实时荧光定量PCR及免疫组织化学法检测癌组织及癌旁组织中R-spondin 1~4及β-链蛋白(β-catenin)的mRNA 及蛋白表达情况；分析R-spondin 1~4表达水平与结直肠癌的临床病理因素之间的关系；探讨R-spondin 1~4与β-catenin 在结直肠癌中表达的相关性。结果：与癌旁组织相比较，R-spondin 1蛋白及mRNA在结直肠癌组织中呈高表达 (P<0.05)；与正常组织比较，R-spondin 2~4在结直肠癌组织中呈高表达，但与癌旁组织的表达水平比较差异无统计学 意义(P>0.05)；结直肠癌组织中R-spondin 1表达水平与β-catenin的细胞核表达水平呈正相关(r=0.6307，P<0.05)。结论： 与癌旁组织相比较，R-spondin 1在结直肠癌组织中呈高表达；R-spondin 1可能通过调控Wnt信号通路下游的β-catenin活 性而发挥促癌作用。

Expression of regulatory factor R-spondin family in Wnt signaling pathway in colorectal cancer and its clinical significance

Objective: To explore the expression of R-spondin family in colorectal cancer tissues and adjacent tissues, and to evaluate its relationship with clinic-pathological stage. Methods: A total of 64 samples of colorectal cancer tissues and adjacent tissues were collected from the patients, who received radical surgery in Xiangya Hospital, Central South University between January 2014 and August 2014. Th e mRNA and protein expression levels of R-spondin 1–4 and β-catenin in the colorectal cancer tissues and adjacent tissues were detected by qRT-PCR and immunohistochemistry. The relationship between the expression level of R-spondin 1–4 and the clinic-pathological factors were analyzed to explore the correlation between the expression level of R-spondin 1–4 and β-catenin in colorectal cancer. Results: Compared with the adjacent tissues, the mRNA and protein expression levels of R-spondin 1 were elevated in the colorectal cancer tissues (P<0.05). The mRNA and protein expression levels of R-spondin 2–4 were increased in the colorectal cancer tissues than those in the normal tissues (P<0.05), but there was no significant difference between the colorectal cancer tissues and adjacent tissues (P>0.05). The expression level of R-spondin 1 was positively correlated with the nuclear expression of β-catenin in the colorectal cancer tissues (r=0.6307, P<0.05). Conclusion: Compared with the adjacent tissues, the mRNA and protein expression levels of R-spondin 1 are significantly elevated in the colorectal cancer tissues. R-spondin 1 may play a role in promoting carcinogenesis by regulating the activity of β-catenin in the downstream of Wnt signaling pathway.