PIK3CA、PTEN基因突变与结直肠癌的肝转移发生及预后关系的临床研究  

A study of the relationship between the mutation of PIK3CA, PTEN and the occurrence of liver metastasis of colorectal cancer： survival analysis

作　　者：梁立[1] 韦烨[1] 任黎[1] 钟芸诗[1] 许剑民[1] 

机构地区：[1]复旦大学附属中山医院普外科复旦大学普通外科研究所,上海200032

出　　处：《中华外科杂志》2012年第11期1007-1010,共4页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目（30973416、81101566）;卫生部部属（管）医院临床学科重点项目（2010-2012年度）;上海市卫生局人才基金资助项目（XYQ2011017、XBR2011031）

摘　　要：目的研究结直肠癌肿瘤原发灶中PIK3CA、PTEN基因突变情况与肝转移发生及预后的相关性。方法选取2003-2008年手术治疗的结直肠癌病例300例，根据诊断及随访资料分为三组：无肝转移组、同时性肝转移组和异时性肝转移组。运用Pyrosequencing测序法检测石蜡标本中PIK3CA基因第9、20外显子和FFEN基因第5、7、8外显子突变情况，分析其与肝转移发生和预后的关系。结果300例患者，男性182例、女性118例，结肠癌180例、直肠癌120例，各组临床病理特征差异无统计学意义。结直肠癌肿瘤原发灶PIK3CA基因突变率为18．2％（51／300）、PTEN基因突变率为16．3％（49／300）。多因素分析提示，PTEN第5外显子突变是结直肠癌同时性肝脏转移的独立危险因素之一（HR=1．634，95％CI：1．796～3．355，P=0．041）。在预后方面，同时性肝转移组转移灶切除患者中PTEN基因突变者总体生存率较低（中位时间为62．0、71．0个月，X^2=12．942，P=0．048），而在同时性和异时性肝转移组，肝脏转移切除的患者中，PIK3CA基因突变者无复发生存较差（中位时间为16．0、25．0个月，X^2=9．679，P=0．037）。结论结直肠癌原发灶PTEN基因第5外显子突变可能成为预测肝转移发生因素之一，联合检测PIK3CA、FFEN基因状态能够为预测结直肠癌肝转移手术切除的预后提供一定的帮助。Objective To investigate PIK3CA, PTEN status in the primary lesion of colorectal cancer （CRC） ： relationship with occurrences of liver metastasis and its prognosis. Methods Patients with CRC who had the primary tumor resected between 2003 and 2008 were selected and enrolled into three groups according to the occurrence of liver metastasis. The mutations of PIK3CA exon 9 and 20, PTEN exon 5, 7, 8 in primary cancer cells in formalin-fixed, paraffin-embedded specimens were detected by Pyrosequencing, then a statistical analysis was deduced to find out the relationship between PIK3CA, PTEN status and occurrences of liver metastasis as well as the prognosis. Results Of all the 300 CRC cases, the mutation rates of PIK3CA and PTEN was 18.2% （51/300）and 16. 3% （49/300）. The multivariate Logistic analysis revealed that exon 5 mutation of PTEN was one of the independent risk factors of occurrence of metachronous liver metastasis in CRC patients （HR = 1. 634, 95% CI： 1. 796-3. 355,P = 0. 041 ）. Patients with PTEN mutation had a poorer overall survival in group with synchronous liver metastasis （ median survival time 62. 0 months vs 71.0 months, X^2 = 12. 942, P= 0. 048 ） while CRC patients who had the liver metastasis resected in group of synchronous and metachronous liver metastasis had a poorer disease free survival rates with PIK3CA mutation （median survival time 16. 0 months vs 25.0 months, X^2 =9. 679, P = 0. 037）. Conclusions The exon 5 mutation of PTEN of CRC is potentially correlated with the occmTence of synchronous liver metastasis. CRC patients who had the liver metatasis resected but with PIK3CA mutation could have a poorer prognosis.

关 键 词：结直肠肿瘤 肿瘤转移 日干肿瘤 1-磷脂酰肌醇3-激酶 PTEN磷酸水解酶 突变 预后 

分 类 号：R735.3[医药卫生—肿瘤]