大肠癌组织中KRAS和PIK3CA基因突变关系的研究

Relationship of KRAS and PIK3CA gene mutation in colorectal cancer

目的：分析KRAS/PIK3CA基因突变与临床病理特征如性别、年龄、肿瘤部位、病理类型、组织学分级、TNM分期、淋巴结转移之间的关系,尤其是与大肠癌远处转移之间的关系。方法：收集2012年1月~2015年8月佛山市三水区人民医院胃肠外科切除的大肠癌标本共94例,提取DNA后行KRAS和PIK3CA基因测序;分析其临床病理特征（性别、年龄、肿瘤部位、病理类型、组织学分级、TNM分期、淋巴结转移、远处转移）,剖析KRAS/PIK3CA基因突变与上述因素尤其是与远处转移的关系,并进行统计学分析处理;对患者进行为期3年的随访,观察其发生远处转移和复发的情况,统计其发生例数,并做统计学分析处理。结果：KRAS基因突变与性别、年龄、肿瘤部位、病理类型、组织学分级无关（P〉0.05）,与远处转移、淋巴结转移、TNM分期明显相关（P〈0.05）;PIK3CA与性别、年龄、肿瘤部位、病理类型、组织学分级无关（P〉0.05）,与TNM分期、淋巴结转移、远处转移相关（P〈0.05）;KRAS和PIK3CA共同突变（双阳性）7例（7.4%）,均未突变（双阴性）55例（57.4%）;双阳性中伴有远处转移者5例,转移率为71.4%,高于双阴性（16/55,29.1%）,差异有统计学意义（P=0.039）;随访发现KRAS突变型转移率高于野生型,差异有统计学意义（P〈0.05）;KRAS、PIK3CA突变型复发率高于野生型,差异有统计学意义（P〈0.05）。结论：大肠癌组织中KRAS和PIK3CA基因突变率与TNM分期、淋巴结转移、远处转移相关,突变型较野生型更易发生远处转移或复发;KRAS和PIK3CA基因突变对大肠癌的远处转移和复发可能有一定的预测价值,对判断患者预后有一定的指导意义。

Objective：To analyze the relationship between KRAS/PIK3 CA gene mutation and clinicopathologic characteristics such as gender,age,tumor location,pathological pattern,histological grade,TNM stage and lymph node metastasis,especially the relationship with distant metastasis of colorectal cancer.Methods：A total of 94 cases of colorectal cancer samples surgically resected in Gastrointestinal Surgery Department of our hospital from January 2012 to August 2015 were collected,DNA was extracted and then KRAS and PIK3 CA gene sequencing was carried out;their clinicopathologic characteristics（gender,age,tumor location,pathological pattern,histological grade,TNM stage,lymph node metastasis and distant metastasis）were analyzed,the relationship between KRAS/PIK3 CA gene mutation and above factors,especially distant metastasis was analyzed,and statistical analysis processing was conducted;patients received 3-year follow-up,distant metastasis and recurrence were observed,and the number of their cases was counted,statistically analyzed and processed.Results：KRAS gene mutation was not associated with gender,age,tumor location,pathological pattern and histological grade（P〈0.05）,and significantly associated with distant metastasis,lymph node metastasis and TNM stage（P〈0.05）;PIK3CA was not associated with gender,age,tumor location,pathological pattern and histological grade（P〈0.05）,and associated with TNM stage,lymph node metastasis and distant metastasis（P〈0.05）;7cases（7.4%）were with mutation of both KRAS and PIK3CA（double positive）,and 55cases（57.4%）were with no mutation at all（double negative）;in double positive cases,5cases were with distant metastasis,metastasis rate was 71.4%and higher than that of double negative（16/55,29.1%）,and there were statistical differences（P=0.039）;it was found in follow-up that metastasis rate of KRAS mutant type was higher than that of wild type,and differences were statistically significant（P〈0.05）;recurrence rates of KRAS and PIK3 CA mutant type were higher than those of wild type,and differences were statistically significant（P〈0.05）.Conclusions：KRAS and PIK3 CA gene mutation rates in colorectal cancer tissue are associated with TNM stage,lymph node metastasis and distant metastasis,and mutant type is more susceptible to distant metastasis and recurrence than wild type;KRAS and PIK3 CA gene mutation may have certain predictive value for distant metastasis and recurrence of colorectal cancer,and have certain guiding significance for judgment of patients＇ prognosis.