miR-221/miR-222及c-KIT在胃肠道间质瘤中的表达及临床意义

Expression and clinical significance of miR-221/miR-222 and c-KIT in gastrointestinal stromal tumors

目的 研究miR-221/miR-222及c-KIT在胃肠道间质瘤(GIST)组织中的表达特点以及与临床病理特征的关系。方法 收集连云港市第二人民医院胃肠外科2020年1月至2022年1月经外科手术切除的GIST病理组织标本89例作为GIST组,另外收集其他胃肠道肿瘤组织16例和正常胃肠道黏膜组织15例分别作为其他肿瘤组和黏膜对照组,采用实时荧光定量PCR(qPCR)法检测组织中miR-221/miR-222表达,Sanger测序法检测c-KIT基因突变情况,并分析miR-221/miR-222表达与患者临床病理特征、c-KIT基因突变、CD117表达的相关性。结果 64例(71.91%)GIST组织检测出c-KIT突变,其中8例(12.50%)存在9号外显子突变,52例(81.25%)存在11号外显子突变,4例(6.25%)存在13号外显子突变。GIST组组织中miR-221(0.69±0.25)和miR-222表达量(0.71±0.21)均显著低于黏膜对照组(1.00±0.26;1.00±0.26)和其他肿瘤组(0.97±0.29;0.96±0.18),差异有统计学意义(P<0.001)。CD117IHC+组织中miR-221/miR-222表达量较CD117IHC-组织显著降低(0.63±0.23 vs. 0.89±0.20,P<0.001;0.67±0.21 vs. 0.83±0.19,P=0.004);然而c-KIT MUT组织和c-KIT WT组织中miR-221/miR-222表达量比较差异无统计学意义(P>0.05)。随着肿瘤直径增加、核分裂相(50高倍视野下)增加以及NIH危险分级增加,组织miR-221/miR-222表达逐渐降低(P<0.001)。结论 GIST患者肿瘤组织中miR-221/miR-222表达水平下调,并且与CD117表达、GIST肿瘤直径、核分裂相和NIH危险分级有关。

Objective To investigate the expression characteristics of miR-221/miR-222 and c-KIT in gastrointestinal stromal tumors(GIST)and their relationship with clinicopathological features.Methods A total of 89 cases of pathological tissue samples of GIST removed by surgical operation from the Department of Gastrointestinal Surgery of the Second People s Hospital of Lianyungang City from January 2020 to January 2022 were collected as GIST group,and 16 cases of other gastrointestinal tumors and 15 cases of normal gastrointestinal mucosal tissues were collected as other tumor group and mucosal control group,respectively.Real-time quantitative fluorescent PCR(qPCR)was used to detect the expression of miR-221/miR-222 in tissues,and Sanger sequencing was used to detect the mutation of c-KIT gene,and the correlation between the expression of miR-221/miR-222 and the clinicopathological features,c-KIT gene mutation and CD117 expression of patients was analyzed.Results c-KIT mutations were detected in 64 cases(71.91%)of GIST tissues,of which 8 cases(12.50%)had exon 9 mutations,52 cases(81.25%)had exon 11 mutations,and 4 cases(6.25%)had exon 13 mutations.The expression levels of miR-221(0.69±0.25)and miR-222(0.71±0.21)in GIST group were significantly lower than those in mucosal control group(1.00±0.26;1.00±0.26)and other tumor groups(0.97±0.29;0.96±0.18),the difference was statistically significant(P<0.001).The expression levels of miR-221/miR-222 in CD117IHC+tissues were significantly lower than those in CD117IHC-tissues(0.63±0.23 vs.0.89±0.20,P<0.001;0.67±0.21 vs.0.83±0.19,P=0.004);However,there was no significant difference in the expression levels of miR-221/miR-222 between c-KIT MUT and c-KIT WT(P>0.05).The expression of miR-221/miR-222 decreased gradually with the increase of tumor diameter,mitotic phase(50 high-power field of view)and NIH risk grade(P<0.001).Conclusion The expression level of miR-221/miR-222 is down-regulated in GIST patients,which is related to CD117 expression,GIST tumor diameter,mitotic phase and NIH risk grade.