KRAS基因突变对中晚期原发性肝癌患者经DEB-TACE治疗后生存期的预测价值  

The predictive value of KRAS gene mutation for survival after DEB-TACE treatment in patients with middle and advanced primary hepatic carcinoma

作　　者：徐颖 季汉超 张海军[1] 徐静 XU Ying;JI Han-chao;ZHANG Hai-jun;XU Jing(Department of Pharmacy,Yancheng Third People's Hospital,Jiangsu 224000,China)

机构地区：[1]盐城市第三人民医院药学部,江苏224000

出　　处：《肝脏》2024年第9期1047-1051,共5页Chinese Hepatology

基　　金：2021盐城市医药科技发展规划项目(YK2021060)。

摘　　要：目的 探讨Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)基因突变对中晚期原发性肝癌(PHC)患者经药物微球经肝动脉化疗栓塞(DEB-TACE)治疗后生存期的预测价值。方法 回顾性分析2020年1月至2022年1月收治的158例行DEB-TACE治疗的中晚期PHC患者的临床资料,DEB-TACE前均已获取肿瘤组织标本并石蜡包埋,检测KRAS基因突变状态,分析KRAS基因突变状态与患者临床病理特征、DEB-TACE近期疗效及预后生存期的关系。结果 158例患者中检出携带KRAS基因突变的有41例(25.95%),其中2号外显子(exon 2)第12密码子突变38例,第13密码子突变3例。KRAS基因突变与患者肿瘤分化程度、中国肝癌分期(CNLC)、AFP水平、肝内转移明显相关(均P<0.05)。突变型(KRAS-MT)患者的DEB-TACE治疗客观缓解率(ORR)、疾病控制率(DCR)明显低于野生型(KRAS-WT)患者,分别为31.71%(13/41)比71.79%(84/117)和68.29%(28/41)比86.32%(101/117),差异均有统计学意义(均P<0.05)。受试者工作特征(ROC)曲线分析显示,KRAS基因突变状态预测DEB-TACE疗效的灵感度为78.80%,特异度为76.40%,曲线下面积为0.873(95%CI:0.764~0.936)。KRAS-MT患者中位总生存期(OS)短于KRAS-WT患者(P<0.001)。多因素Cox风险回归分析结果显示,肿瘤低分化(OR=2.014)、CNLC分期Ⅲa期(OR=4.742)、有肝内转移(OR=3.861)、KRAS-MT(OR=5.137)的患者在接受DEB-TACE治疗后死亡风险较大(均P<0.05)。结论 KRAS基因突变与中晚期PHC患者DEB-TACE近期疗效和预后生存期有关,可作为DEB-TACE疗效和预后生存期的预测指标。Objective To investigate the predictive value of Kirsten rat sarcoma viral oncogene homolog(KRAS)gene mutation in patients with middle and advanced primary hepatic carcinoma(PHC)treated by drug‐eluting beads transarterial chemoembolization(DEB-TACE).Methods The clinical data of 158 patients with middle and advanced PHC treated with DEB-TACE from January 2020 to January 2022 were retrospectively analyzed.Tumor tissue samples were obtained and paraffin embedded before DEB-TACE,and KRAS gene mutation status was detected.The relationship between the mutation status of KRAS gene and clinicopathological features,the short-term efficacy of DEB-TACE and the prognosis of the patients was analyzed.Results Among 158 patients,KRAS gene mutation was detected in 41 cases(25.95%),all mutations were in exon 2,including 38 patients with codon 12 mutation and 3 patients with codon 13 mutation.KRAS gene mutation was significantly correlated with tumor differentiation,China liver cancer staging(CNLC),AFP level,and intrahepatic metastasis(all P<0.05).The DEB-TACE objective response rate(ORR)(31.71%vs.71.79%)and disease control rate(DCR)(68.29%vs.86.32%)of patients with mutant type(KRAS-MT)were significantly lower than those with wild-type(KRAS-WT)(both P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity and specificity of KRAS mutation status in predicting DEB-TACE efficacy were 78.80%and 76.40%,and the area under the curve(AUC)was 0.873(P=0.000,95%CI:0.764~0.936).The median overall survival(OS)in KRAS-MT patients was shorter than that in KRAS-WT patients(P<0.001).Multivariate Cox risk regression analysis showed that patients with low tumor differentiation(OR=2.014),CNLC stageⅢa(OR=4.742),intrahepatic metastasis(OR=3.861),and KRAS-MT(OR=5.137)had a higher risk of death after DEB-TACE treatment(all P<0.05).Conclusion KRAS gene mutation is associated with the short-term efficacy and prognosis of DEB-TACE in patients with middle and advanced PHC,and can be used as a predictor of DEB-TACE efficacy

关 键 词：KRAS基因 原发性肝癌 DEB-TACE 预后生存期 

分 类 号：R735.7[医药卫生—肿瘤]