摘要
目的:探讨结直肠癌中鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)突变和B淋巴细胞瘤2(B-cell lymphoma-2,Bcl-2)、半胱氨酸天冬氨酸蛋白酶3(cysteine aspartase-3,caspase-3)表达的相关性,以及它们与结直肠癌临床病理参数及患者预后的关系。方法:收集116例结直肠癌患者的肿瘤组织,采用二代测序技术检测KRAS基因突变状态,实时荧光定量PCR及免疫组织化学法分别检测Bcl-2和caspase-3的mRNA及蛋白表达水平。然后采用Spearman法分析KRAS基因突变与Bcl-2和caspase-3蛋白表达的相关性,采用χ2检验和Kaplan-Meier法分别分析KRAS基因突变、Bcl-2和caspase-3表达与结直肠癌临床病理特征及患者生存时间的关系。结果:116例结直肠癌组织中KRAS基因突变率为42.2%(49/116)。KRAS基因突变的结直肠癌组织中,Bcl-2 mRNA表达强度较KRAS野生型组明显增高(P <0.001),而caspase-3 mRNA表达强度明显降低(P <0.001)。KRAS基因突变与结直肠癌淋巴结转移、术前血清癌胚抗原(carcinoembryonic antigen,CEA)水平及TNM分期相关(P值均<0.05),Bcl-2蛋白表达与肿瘤分化程度、TNM分期、术前血清CEA水平及淋巴结转移有关(P值均<0.05),而caspase-3蛋白表达与肿瘤分化程度及CEA水平相关(P值均<0.05)。KRAS基因突变与Bcl-2蛋白表达呈正相关关系(rs=0.428,P <0.001),而与caspase-3蛋白表达呈负相关关系(rs=-0.206,P=0.027);Bcl-2与caspase-3 mRNA表达呈负相关关系(rs=-0.551,P <0.001)。KRAS基因野生型患者的总生存时间较KRAS突变型患者明显延长(χ2=53.19,P <0.001);Bcl-2阳性表达患者的总生存时间较Bcl-2阴性表达者明显缩短(χ2=40.36,P <0.001),而caspase-3阳性表达患者的总生存时间较caspase-3阴性表达者明显延长(χ2=31.98,P <0.001)。KRAS基因突变型患者中,Bcl-2阳性表达患者的总生存时间较Bcl-2阴性表达者明显缩短(χ2=13.94,P=0.002),而caspase-3阳性表达患者的总生存时间较caspase-3阴性表达者明显�
Objective: To investigate the correlations between kirsten rat sarcoma viral oncogene(KRAS)mutation and the expressions of B-cell lymphoma-2(Bcl-2) and cysteine aspartase-3(caspase-3) in colorectal cancer, and to explore their relationship with the clinicopathological parameters and prognosis of colorectal cancer patients.Methods: A total of 116 colorectal cancer tissues were collected. The mutation status of KRAS gene was detected by second-generation sequencing method. The expressions of Bcl-2 and caspase-3 mRNA and protein were detected by real-time fluorescent quantitative PCR and immunohistochemical method, respectively. The correlations between KRAS gene mutation and the expressions of Bcl-2 and caspase-3 proteins were analyzed by Spearman mothod,and their relationships with the clinicopathological characteristics and survival time of colorectal cancer patients were analyzed by χ 2 test and Kaplan-Meier method, respectively.Results: The mutation rate of KRAS gene was 42.2%(49/116) in 116 cases of colorectal cancer.The expression level of Bcl-2 in KRAS mutant patients was significantly higher than that in KRAS wild-type patients(P < 0.001). The expression level of caspase-3 in KRAS mutant patients was significantly lower than that in KRAS wild-type patients(P < 0.001). The mutation of KRAS gene was correlated with lymph node metastasis, preoperative serum carcinoembryonic antigen(CEA)level and TNM stage of colorectal cancer(all P < 0.05). The expression of Bcl-2 protein was correlated with the degree of tumor differentiation, TNM stage, preoperative serum CEA level and lymph node metastasis of colorectal cancer(all P < 0.05). The expression of caspase-3 protein was correlated with the degree of tumor differentiation and preoperative serum CEA level(both P < 0.05).KRAS mutation was positively correlated with Bcl-2 protein expression( rs = 0.428, P < 0.001), and negatively correlated with caspase-3 protein expression( rs =-0.206, P = 0.027). The expression of Bcl-2 mRNA was negatively correlated with caspase-
作者
刘云
段芳蕾
李霞斌
郭庆喜
陈芊杏
冯健
孙兴旺
LIU Yun;DUAN Fanglei;LI Xiabin;GUO Qingxi;CHEN Qianxing;FENG Jian;SUN Xingwang(Department of Pathology, College of Basic Medicine, Southwestern Medical University, Luzhou 646000, Sichuan Province, China;Department of Pathology, Sichuan Cancer Hospital & Institute, Chengdu 610041, Sichuan Province, China;Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China;Department of Cardiovascular Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China)
出处
《肿瘤》
CAS
CSCD
北大核心
2019年第3期204-214,共11页
Tumor
