EBV相关性胃癌患者血浆miRNAs表达谱的研究

Profiling of plasma EBV-miRNAs in EBV-associated gastric carcinomas

目的探讨EBV相关性胃癌(EBV-associated gastric carcinomas,EBVaGCs)患者血浆中EBV-miRNAs表达水平及其临床意义。方法收集226例胃癌患者和56例非EBV感染相关的肿瘤患者外周血,采用RT-PCR检测EBV-DNA,荧光定量Real-time RTPCR分析EBV-miRNAs表达谱,结合组织病理和影像学检查结果分析这些miRNAs的临床意义。结果在胃癌患者中,有177例EBV阴性胃癌和49例EBVaGCs患者。在EBVaGCs中,EBV-miR-BART5的表达水平是RNU6B的3.5倍,而EBV-miR-BART1、miRBART1-2、miR-BART7及miR-BART10分别为2.4、2.0、3.1、2.9倍。EBV-miRNAs在低分化胃癌中均高表达,EBV-miR-BART5和miR-BART7在中高分化胃癌表达差异具有统计学意义(P<0.05),但EBV-miR-BART1、miR-BART1-2和miR-BART10表达差异无统计学意义(P>0.05)。85.7%(42/49)EBVaGCs患者二程化疗后症状缓解,12.2%(6/49)局部侵袭,2.0%(1/49)淋巴结转移;而64.4%(114/177)EBV阴性胃癌患者二程化疗症状缓解,20.3%(36/177)局部侵袭,10.7%(19/177)淋巴结转移,4.5%(8/177)远处转移。结论 EBV-miR-BART5和miR-BART7可作为EBVaGCs无创诊断、治疗和预后的生物标志物;EBVaGCs患者预后比EBV阴性胃癌好。

Objective To study the expression and clinical significance of plasma EBV-miRNAs in patients with EBV-associated gastric carcinomas （EBVaGCs）. Methods Plasma of 226 gastric cancer patients and 56 cancer pa- tients with EBV negative were collected. EBV-DNA was detected by RT-PCR, plasma level of EBV-miRNAs was deter- mined by fluorescence quantitative Real-time PCR, and the clinical significance of these miRNAs combined with his- topathological and imaging examination was analyzed. Results There were 177 cases of EBV-negative gastric cancer and 49 cases of EBVaGCs. The expression of EBV-miR-BART5 was 3.5 times higher than that of RNU6B in EBVaGCs, while the expression of EBV-miR-BART1, miR-BART1-2, miR-BART7 and miR-BART10 were 2.4, 2.0, 3.1 and 2.9 times, respectively. EBV-miRNAs were highly expressed in poorly differentiated gastric cancer, and the expression of EBV-miR-BART5 and EBV-miR-BART7 showed a statistically significant difference in well-differentiated gastric cancer （P 〈 0.05）, however, the difference of EBV-miR-BART1 , miR-BART1-2 and miR-BARTI0 expression in well-differ- entiated gastric cancer had no significant difference （P 〉 0.05）. The clinical symptoms of 85.7% （42/49） patients with EBVaGCs were relieved after two-way chemotherapy, local invasion was found in 12.2% （6/49） patients and lymph node metastasis was found in 2.0% （1/49） patients; however, the clinical symptoms were alleviated in 64.4% （114/177） patients with EBV negative gastric after two-way chemotherapy, 20.3% （36/177） patients were found with locally invasive, 10.7% （19/177） with lymph node metastasis and 4, 5% （8/177） with distant metastasis. Conclu- sion EBV-miR-BART5 and EBV-miR-BART7 could be used as the biomarkers of non-invasive diagnosis, treatment and prognosis in EBVaGCs. EBVaGCs shows a relatively better prognosis than EBV-negative gastric carcinomas.