血清外泌体miR-27a在胃癌中的表达及其临床意义
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摘要
目的外泌体近年来成为肿瘤研究中关注的热点,外泌体中的miRNA已经证实在多种肿瘤中发挥重要作用。本研究旨在探讨胃癌患者血清外泌体microRNA-27a的表达变化及其临床意义。方法收集40例在2015年1月—2017年12月间就诊于安徽医科大学第二附属医院普外科且前期没有接受过任何治疗的胃癌患者术前术后血清标本,收集同期20例体检健康者血清标本,分离血清外泌体,同时进行RNA提取。采用实时荧光定量聚合酶链反应(qRT-PCR)检测血清外泌体miR-27a水平的相对定量含量,比较胃癌组与正常组之间的差异,并比较胃癌组术前、术后外泌体miR-27a表达的差异。对40例胃癌患者血清外泌体miR-27a水平以及临床病理表现(性别、年龄以及肿瘤分级)进行分析,在参照随访资料的基础上,分析患者外泌体miR-27a表达与预后间的联系。结果胃癌患者术前血清外泌体miR-27a水平为0.153±0.092,健康体检者为0.823±0.125,两者比较差异有统计学意义(P<0.001);胃癌患者术后血清外泌体miR-27a水平为0.505±0.143,与术前比较明显升高(P<0.05)。肿瘤患者血清外泌体miR-27a表达量与肿瘤分级成负相关,Ⅰ/Ⅱ期患者术前相对表达量为0.179±0.102,Ⅲ/Ⅳ期为0.102±0.076(P<0.05)。结论胃癌患者血清外泌体中miR-27表达量明显降低,其表达量与肿瘤分级负相关,对于早期筛查胃癌和胃癌的治疗有一定的临床价值。
Objective The exosome has absorbed much attention in the study of cancers in recent years, and exosomal miRNAs have been validated to play important roles in variety of tumors. This study aimed to invest the serum exosomal miRNA-27a expression and its significance in gastric cancer. Methods By using real-time fluorescence quantitative PCR(QPCR), the serum exosomal miRNA-27a levels of both 40 gastric cancer and 20 normal people who were cured in our hospital from January 2015 to December 2017 were investigated; the serum exosomal miR-27a expression levels between the cancer group and control group were compared. Meanwhile, the change of serum exosomal miR-27a expression level of the 40 patients after the operation was compared with that before the surgery. The relevance of the expression level of serum exosomal miR-27a to the clinical pathological characteristics(sex, age and tumor grade) was invested, and the relationship between serum miR-27a and the prognosis of patients were analyzed based on the follow-up information.Results The serum exosomal miR-27a expression level of the 40 patients(0.153±0.092, before the surgery) was significantly lower than that of 20 normal control(0.823±0.125), the difference was statistically significant(P<0.001). After the operation, the level of serum exosomal miR-27a expression was 0.505±0.143, which was definitely up-regulated(P<0.05). Also, the expression level of serum exosomal miR-27a in the Ⅰ/Ⅱ grade patients was 0.179±0.102, and in the Ⅲ/Ⅳ grades patients was 0.102±0.076(P<0.05), which revealed that the expression level of serum exosomal miR-27a was negatively correlated with the tumor grade in gastric cancer.Conclusion The expression level of miRNA-27a is definitely down regulated in gastric cancers and negatively correlated with its grade. The test of serum miR-27a level can provide an innovative target for the early scanning and treatments of gastric cancer.
Objective The exosome has absorbed much attention in the study of cancers in recent years, and exosomal miRNAs have been validated to play important roles in variety of tumors. This study aimed to invest the serum exosomal miRNA-27a expression and its significance in gastric cancer. Methods By using real-time fluorescence quantitative PCR(QPCR), the serum exosomal miRNA-27a levels of both 40 gastric cancer and 20 normal people who were cured in our hospital from January 2015 to December 2017 were investigated; the serum exosomal miR-27a expression levels between the cancer group and control group were compared. Meanwhile, the change of serum exosomal miR-27a expression level of the 40 patients after the operation was compared with that before the surgery. The relevance of the expression level of serum exosomal miR-27a to the clinical pathological characteristics(sex, age and tumor grade) was invested, and the relationship between serum miR-27a and the prognosis of patients were analyzed based on the follow-up information.Results The serum exosomal miR-27a expression level of the 40 patients(0.153±0.092, before the surgery) was significantly lower than that of 20 normal control(0.823±0.125), the difference was statistically significant(P<0.001). After the operation, the level of serum exosomal miR-27a expression was 0.505±0.143, which was definitely up-regulated(P<0.05). Also, the expression level of serum exosomal miR-27a in the Ⅰ/Ⅱ grade patients was 0.179±0.102, and in the Ⅲ/Ⅳ grades patients was 0.102±0.076(P<0.05), which revealed that the expression level of serum exosomal miR-27a was negatively correlated with the tumor grade in gastric cancer.Conclusion The expression level of miRNA-27a is definitely down regulated in gastric cancers and negatively correlated with its grade. The test of serum miR-27a level can provide an innovative target for the early scanning and treatments of gastric cancer.
引文
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[13] 唐慧,伍海姗,杨怡,等.外泌体源性microRNA在疾病诊疗中的研究进展[J].中南大学学报(医学版),2015,40(11):1270-1275.
[14] REN J,ZHOU Q,LI H,et al.Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing[J].Tumour Biol,2017,39(4):1010428317695012.
[15] 酒梦娜.Effects of human microRNA-181a-5p on proliferation and migration of gastric cancer cells[J].China Medical Abstracts(Internal Medicine),2016,33(3):167-168.
[2] PEI H,JIN Z,CHEN S,et al.MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1[J].Mol Cell Biochem,2015,400(1-2):245-252.
[3] 耿威,仉慧颖,李林,等.miRNA-21调控胃癌细胞增殖及侵袭的机制[J].中国老年学杂志,2018,38(2):271-273.
[4] SHAO Y,YE M,LI Q,et al.LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer[J].Oncotarget,2016,7(25):37812-37824.
[5] K?HLER J,SCHULER M,GAULER T C,et al.Circulating U2 small nuclear RNA fragments as a diagnostic and prognostic biomarker in lung cancer patients[J].J Cancer Res Clin Oncol,2016,142(4):795-805.
[6] CHANDRA N K,SINGH R,BHATTACHARYA S.A Novel Bayesian Multiple Testing Approach to Deregulated miRNA Discovery Harnessing Positional Clustering[J].Biometrics,2019,75(1):202-209.
[7] 吴彩云,张春妮.MicroRNA与神经胶质瘤关系的研究进展[J].医学研究生学报,2014,27(7):746-750.
[8] HUMPHREYS K J,CONLON M A,YOUNG G P,et al.Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa:A Randomized Trial[J].Cancer Prev Res(Phila),2014,7(8):786-795.
[9] 许新才,林海,张旺,等.胃癌组织中miRNA-21和miRNA-34的表达及其意义[J].新疆医科大学学报,2016,39(7):854-857.
[10] ACUNZO M,CROCE C M.MicroRNA in cancer and cachexia-a mini review[J].J Infect Dis,2015,212(Suppl 1):S74-S77.
[11] UM M H,CHOI M Y,LEE S M,et al.Intensive nutritional counseling improves PG-SGA scores and nutritional symptoms during and after radiotherapy in Korean cancer patients[J].Support Care Cancer,2014,22(11):2997-3005.
[12] 张敏,张晨光,丁卫.外泌体及其在肿瘤诊疗中的意义[J].生理科学进展,2014,45(5):372-378.
[13] 唐慧,伍海姗,杨怡,等.外泌体源性microRNA在疾病诊疗中的研究进展[J].中南大学学报(医学版),2015,40(11):1270-1275.
[14] REN J,ZHOU Q,LI H,et al.Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing[J].Tumour Biol,2017,39(4):1010428317695012.
[15] 酒梦娜.Effects of human microRNA-181a-5p on proliferation and migration of gastric cancer cells[J].China Medical Abstracts(Internal Medicine),2016,33(3):167-168.