胃癌组织微小RNA-181d-5p和三基序蛋白22表达与患者术后5年内生存相关性研究

Correlation between miR-181d-5p,TRIM22 expression in gastric cancer tissues and 5-year postoperative survival of patients

目的:探讨胃癌组织微小RNA-181d-5p(miR-181d-5p)和三基序蛋白22(TRIM22)表达与患者术后5年内生存的关系。方法:收集110例胃癌患者(均是胃腺癌)术中切除的胃癌组织标本及癌旁组织标本。荧光定量PCR和免疫组织化学法分别检测miR-181d-5p和TRIM22蛋白表达。患者术后随访5年,记录生存情况。Starbase数据库预测miR-181d-5p与TRIM22结合位点,并验证miR-181d-5p与TRIM22的靶向关系。比较癌旁和胃癌组织miR-181d-5p、TRIM22表达,不同临床病理特征患者胃癌组织miR-181d-5p、TRIM22表达差异。分析胃癌组织miR-181d-5p、TRIM22表达与患者预后的关系,胃癌患者预后的影响因素,以及胃癌组织miR-181d-5p与TRIM22及它们与不同临床病理特征的相关性。结果:与癌旁组织比较,胃癌组织miR-181d-5p表达升高,TRIM22阳性率降低(均P<0.05)。肿瘤低分化、肌层或外膜浸润、有淋巴结转移、TNM分期Ⅲ期在miR-181d-5p高表达和TRIM22阴性表达患者中的比例分别高于肿瘤高分化、黏膜或膜下层浸润、无淋巴结转移、TNM分期Ⅰ-Ⅱ期(均P<0.05)。miR-181d-5p与TRIM22具有靶向结合位点,miR-181d-5p可负向调控TRIM22表达。miR-181d-5p高表达和TRIM22阴性表达患者5年总生存率分别低于miR-181d-5p低表达和TRIM22阳性表达患者(均P<0.05)。影响胃癌患者术后5年内生存的独立危险因素有miR-181d-5p高表达、TRIM22阴性表达、肿瘤低分化、肌层或外膜浸润、有淋巴结转移和TNM分期Ⅲ期(均P<0.05)。胃癌组织miR-181d-5p与TRIM22、肿瘤分化程度呈负相关,与浸润深度、淋巴结转移、TNM分期呈正相关(均P<0.05);TRIM22与肿瘤分化程度呈正相关,与浸润深度、淋巴结转移、TNM分期呈负相关(均P<0.05)。结论:胃癌组织miR-181d-5p表达升高,TRIM22阳性率降低,两者与患者临床病理特征和术后5年内生存有密切关系。

Objective:To investigate the relationship between the expression of microRNA-181d-5p(miR-181d-5p),tripartite motif protein 22(TRIM22)in gastric cancer tissues and the 5-year postoperative survival of patients.Methods:Gastric cancer tissue specimens and paracancer tissue specimens were collected from 110 patients with gastric cancer(all gastric adenocarcinoma).The expression of miR-181d-5p and TRIM22 protein were detected by RT-qPCR and immunohistochemistry,respectively.the patients were followed up for 5 years after surgery and their survival status were recorded.The binding sites of miR-181d-5p and TRIM22 were predicted by Starbase database,and the targeting relationship between miR-181d-5p and TRIM22 was verified.The expressions of miR-181d-5p and TRIM22 in adjacent tissues and gastric cancer tissues,and the expressions of miR-181d-5p and TRIM22 in gastric cancer tissues of patients with different clinicopathological characteristics were compared.The relationship between the expressions of miR-181d-5p and TRIM22 in gastric cancer tissues and the prognosis of gastric cancer patients,the influencing factors of gastric cancer patients’prognosis,and the correlation of miR-181d-5p and TRIM22 with tumor differentiation,invasion depth,lymph node metastasis and TNM stage were analyzed.Results:Compared with paracancerous tissue,the expression level of miR-181d-5p in gastric cancer tissue was increased,while the positive expression rate of TRIM22 were decreased(all P<0.05).The proportion of patients with low tumor differentiation,muscle layer or outer membrane invasion,lymph node metastasis and TNM stageⅢin high expression of miR-181d-5p and negative expression of TRIM22 were higher than those with tumor with medium and high differentiation,mucosa or submucosa invasion,no lymph node metastasis,TNM stageⅠ-Ⅱ,respectively(all P<0.05).MiR-181d-5p has a targeted binding site with TRIM22,and miR-181d-5p could negatively regulate TRIM22 expression.The 5-year overall survival rate of patients with miR-181d-5p high expression and TRIM22 negative expression were lower than those of patients with miR-181d-5p low expression and TRIM22 positive expression,respectively(all P<0.05).High expression of miR-181d-5p,negative expression of TRIM22,low tumor differentiation,muscle layer or outer membrane invasion,lymph node metastasis,and TNM stageⅢwere all independent risk factors affecting the survival of gastric cancer patients within 5 years after surgery(all P<0.05).MiR-181d-5p in gastric cancer tissue was negatively correlated with TRIM22 and tumor differentiation degree,and positively correlated with infiltration depth,lymph node metastasis,and TNM stage(all P<0.05).TRIM22 was positively correlated with tumor differentiation,but negatively correlated with infiltration depth,lymph node metastasis,and TNM stage(all P<0.05).Conclusion:The expression of miR-181d-5p is increased and the positive rate of TRIM22 is decreased in gastric cancer tissues,which are closely related to the clinicopathological characteristics and 5-year survival of patients.