癌组织M6A甲基转移酶样蛋白3水平对手术切除后接受索拉非尼治疗的肝细胞癌患者预后的影响

Prognosis of patients with hepatocellular carcinoma after hepatectomy and sorafenib therapy: prediction by cancerous M6A methyltransferase-like protein 3 levels

目的探讨肝细胞癌(HCC)组织N 6-甲基嘌呤(M6A)甲基转移酶样蛋白3(METTL3)水平及其对术后索拉非尼治疗的患者预后的预测价值。方法2016年8月~2019年8月我院手术切除治疗的HCC患者62例,随访2年。采用qRT-PCR法检测癌组织和癌旁组织METTL3 mRNA水平,应用受试者工作特征曲线(ROC)下面积(AUC)分析癌组织METTL3 mRNA水平对患者预后的预测价值。结果癌组织METTL3 mRNA水平为(7.7±1.4),显著高于癌旁组织【(5.3±1.1),P<0.05】;肿瘤直径≥5 cm、TNMⅢ期和肝外转移患者癌组织METTL3 mRNA水平分别为(8.1±1.1)、(8.2±1.4)和(8.6±0.8),显著高于肿瘤直径<5 cm、TNMⅠ/Ⅱ期和无肝外转移患者【分别为(7.0±0.9)、(7.3±0.7)和(7.4±1.2),P<0.05】;在随访2年末,HCC患者生存27例,死亡35例;生存组癌组织METTL3 mRNA水平为(7.0±1.0),显著低于死亡组【(8.2±1.1),P<0.05】;以METTL3 mRNA水平为7.6为最佳截断点,预测患者死亡的AUC为0.712【95%CI(0.584~00.839)】,其灵敏度、特异度和准确度分别为71.4%、66.7%和69.4%;癌组织METTL3 mRNA低水平组2 a总体生存率为64.3%,显著高于高水平组的26.5%(P<0.05)。结论肝细胞癌患者癌组织METTL3 mRNA呈现高水平,且其高水平状态与肿瘤直径、TNM分期和肝外转移有关,预示患者不良预后。检测癌组织METTL3 mRNA水平可作为手术切除接受索拉非尼治疗的HCC患者的预后指标。

Objective This study was to explore the prognosis of patients with hepatocellular carcinoma(HCC)after hepatectomy and sorafenib therapy by cancerous N 6-methylpurine(M6A)methyltransferase-like protein 3(METTL3)levels.Methods A total of 62 patients with HCC were enrolled in our hospital between August 2016 and August 2019,and all patients underwent hepatectomy,receiving sorafenib therapy after operation and followed-up for two years.The cancerous and non-cancerous tissue METL3 mRNA levels were detected by qRT-PCR.The prognostic value of cancerous METL3 mRNA was analyzed by area under the receiver operating characteristic(ROC)curves(AUC).Results The cancerous METL3 mRNA level was significantly higher than that in adjacent tissues[(7.7±1.4)vs.(5.3±1.1),P<0.05];the cancerous METL3 mRNA levels in patients with tumor diameter≥5 cm,TNM stageⅢand with extrahepatic metastasis were(8.1±1.1),(8.2±1.4)and(8.6±0.8),all significantly higher than[(7.0±0.9),(7.3±0.7)and(7.4±1.2),P<0.05]in patients with tumor diameter<5 cm,TNM staging stageⅠ-Ⅱand without extrahepatic metastasis(P<0.05);at the end of two-year follow-up,27 patients survived and 35 died;the cancerous METTL3 mRNA level in survived patients was(7.0±1.0),significantly lower than[(8.2±1.1),P<0.05]in died ones;the AUC was 0.712[95%CI(0.584-00.839)]when the optimal cut-off-value of cancerous METTL3 mRNA level was set at 7.6,with the sensitivity,specificity and accuracy of 71.4%,66.7%and 69.4%;the total survival in patients with lower cancerous METTL3 mRNA levels was 64.3%,significantly higher than 26.5%(P<0.05)in those with high cancerous METTL3 mRNA levels.Conclusion The cancerous METTL3 mRNA levels in patients with HCC is up-regulated,and the cancerous METTL3 mRNA level is correlated to tumor diameter,TNM staging and extrahepatic metastasis.The surveillance of cancerous METTL3 mRNA levels might help predict the prognosis of HCC patients receiving sorafenib therapy after hepatectomy.