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

摘要/Abstract

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。

关键词: KRAS基因, 原发性肝癌, DEB-TACE, 预后生存期

Abstract: 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 stage Ⅲa (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 and prognostic survival.

Key words: KRAS gene, Primary hepatic carcinoma, DEB-TACE, Prognostic survival

徐颖, 季汉超, 张海军, 徐静. 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[J]. 肝脏, 2024, 29(9): 1047-1051.

XU Ying, JI Han-chao, ZHANG Hai-jun, XU Jing. The predictive value of KRAS gene mutation for survival after DEB-TACE treatment in patients with middle and advanced primary hepatic carcinoma[J]. Chinese Hepatolgy, 2024, 29(9): 1047-1051.

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