胃癌组织中PRMT5的表达与临床病理特征和预后的关系

Relationship between PRMT5 expression in gastric cancer tissues and clinicopathological features and prognosis

摘要:

目的 探讨胃癌组织中蛋白精氨酸甲基转移酶5（PRMT5）的表达与临床病理特征和预后的关系。方法 选取2016年7月—2018年12月江苏大学附属医院行根治术治疗的123例胃癌患者的胃组织标本。对比胃癌组织和癌旁组织（距癌组织≥ 5 cm）PRMT5 mRNA表达。分析患者癌组织中PRMT5表达与临床病理特征的关系。术后随访3年，统计患者预后情况，分析影响预后的因素。绘制受试者工作特征（ROC）曲线，以曲线下面积（AUC）评价胃癌组织PRMT5-1 mRNA表达对预后的预测价值。依据癌组织中PRMT5表达对胃癌患者预后的最佳截断点，将患者分为PRMT5高表达（≥ 0.74）和PRMT5低表达（< 0.74），分析癌组织中PRMT5表达与患者预后的关系。结果 胃癌组织PRMT5 mRNA表达高于癌旁组织（P <0.05）。不同性别、年龄、BMI、肿瘤直径、浸润深度胃癌患者癌组织中PRMT5 mRNA表达比较，差异无统计学意义（P >0.05）。不同临床分期、病理类型、分化程度、淋巴结转移、远处转移胃癌患者癌组织中PRMT5 mRNA表达比较，差异有统计学意义（P <0.05）。123例胃癌患者术后随访3年，共失访4例，剩余119例患者中32例死亡，病死率26.89%（32/119）。单因素Cox回归分析结果显示，临床分期Ⅲ期［H^R=7.012（95% CI：3.485，8.657）］、低分化［HR=6.285（95% CI：3.027，7.436）］、淋巴结转移［H^R=5.684（95% CI：3.165，8.143）］、远处转移［H^R=6.012（95% CI：3.857，10.245）］、PRMT5表达［H^R=9.436，（95% CI：3.481，12.736）］、病理类型[H^R=5.486（95% CI：2.108，5.436）]、浸润深度[H^R=4.857（95% CI：2.149，6.032）]是胃癌患者预后的危险因素（P <0.05）。多因素Cox回归分析结果显示，临床分期Ⅲ期［H^R=3.031（95% CI：1.965，6.874）］、低分化［H^R=2.838（95% CI：1.042，5.738）］、淋巴结转移［H^R=3.340（95% CI：2.051，8.032）］、远处转移［H^R=3.515（95% CI：2.476，8.543）］、PRMT5表达［H^R=4.035（95% CI：3.008，11.436）］是胃癌患者预后的危险因素（P <0.05）。ROC曲线分析结果显示，胃癌患者癌组织PRMT5表达预测预后的最佳截断点为0.74，敏感性、特异性及AUC分别为78.13%（95% CI：59.56，90.06）、89.66%（95% CI：80.80，94.87）、0.893（95% CI：0.823，0.942）。PRMT5高表达患者预后较PRMT5低表达患者差（P <0.05）。结论 胃癌组织中PRMT5的表达与临床病理特征和预后有关，PRMT5 mRNA高表达胃癌患者生存率较低。

Abstract:

Objective To investigate the relationship between the expression of protein arginine methyltransferase 5 (PRMT5) in gastric cancer tissues and clinicopathological features and prognosis.Methods The gastric tissue samples of 123 gastric cancer patients who underwent radical resections in our hospital from July 2016 to December 2018 were collected. The mRNA expressions of PRMT5 in gastric cancer tissues and adjacent tissues (≥ 5 cm from the cancer tissues) were compared. The relationship between PRMT5 expression and clinicopathological features was analyzed. After 3 years of follow-up, the prognosis of patients was observed and the factors affecting the prognosis of patients with gastric cancer were analyzed. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was used to determine the predictive value of PRMT5-1 mRNA expression in gastric cancer tissues for prognosis of patients. According to the optimal cut-off value of PRMT5 expression in cancer tissues for predicting the prognosis of gastric cancer patients, these patients were divided into PRMT5 high-expression group (≥ 0.74) and PRMT5 low-expression group (< 0.74). The relationship between the expression of PRMT5 in gastric cancer tissues and the prognosis of gastric cancer patients was analyzed.Results The mRNA expression of PRMT5 in gastric cancer tissues was higher than that in adjacent tissues (P < 0.05). There was no difference in the mRNA expression of PRMT5 in cancer tissues among gastric cancer patients with different gender, age, BMI, tumor diameter, pathological patterns of tumors and depth of invasion of tumors (P > 0.05), while the mRNA expression of PRMT5 in cancer tissues was different among patients with different clinical stages and degrees of differentiation of tumors as well as between those with and without lymph node metastasis and distant metastasis (P < 0.05). A total of 123 patients were followed up for 3 years, whereas 4 cases were lost to the follow-up. Among the rest 119 patients, 32 were dead, with the mortality rate being 26.89% (32/119). Univariable Cox regression analysis revealed that stage Ⅲ tumor [H^R= 7.012 (95% CI: 3.485, 8.657) ], poorly-differentiated tumors [H^R = 6.285 (95% CI: 3.027, 7.436) ], lymph node metastasis [H^R = 5.684 (95% CI: 3.165, 8.143) ], distant metastasis [H^R = 6.012 (95% CI: 3.857, 10.245) ], and the expression of PRMT5 [H^R = 9.436 (95% CI: 3.481, 12.736) ] were risk factors for the prognosis of gastric cancer patients (P < 0.05). The multivariable Cox regression analysis showed that stage Ⅲ tumor [H^R = 3.031 (95% CI: 1.965, 6.874) ], poorly-differentiated tumors [H^R=2.838 (95% CI: 1.042, 5.738) ], lymph node metastasis [H^R = 3.340 (95% CI: 2.051, 8.032) ], distant metastasis [H^R = 3.515 (95% CI: 2.476, 8.543) ], and the expression of PRMT5 [H^R = 4.035 (95% CI: 3.008, 11.436) ] (P < 0.05). The ROC curve analysis demonstrated that the optimal cut-off value of the expression of PRMT5 in cancer tissues for predicting the prognosis of gastric cancer patients was 0.74, and the sensitivity, specificity and AUC were 78.13 (95% CI: 59.56, 90.06), 89.66% (95% CI: 80.80, 94.87), and 0.893 (95% CI: 0.823, 0.942), respectively. The prognosis of patients with high expressions of PRMT5 was poorer than that of patients with low expressions of PRMT5 (P < 0.05).Conclusions The expression of PRMT5 in gastric cancer tissues is related to clinicopathological features and prognosis. The survival rate of gastric cancer patients with high mRNA expressions of PRMT5 is lower.