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胃癌组织微小RNA 204-5p、组蛋白赖氨酸甲基转移酶2D与疾病分期、预后的关系

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目的 分析胃癌患者组织中微小RNA 204-5p(miR-204-5p),组蛋白赖氨酸甲基转移酶2D(KMT2D)表达与疾病分期、预后的关系.方法 选取2018年1月至2021年1月武警江苏总队医院120例胃癌患者,检测癌组织及癌旁组织中miR-204-5p、KMT2D表达,分析其与临床病理特征的关系,根据miR-204-5p及KMT2D的表达将患者分为miR-204-5p高表达组(62例)、miR-204-5p低表达组(58例),KMT2D高表达组(57例)、KMT2D低表达组(63例),比较miR-204-5p/KMT2D高表达与低表达组预后,采用受试者工作特征(ROC)曲线分析预后预测效能.组间采用t 检验或单因素方差分析;计数资料以例(%)表示,采用x2检验.结果 癌灶组织miR-204-5p相对表达量(1.78±0.46)低于癌旁组织(2.02±0.53,t=3.746,P<0.05),KMT2D 相对表达量(2.31±0.59)高于癌旁组织(1.88±0.57,t=5.742,P<0.05);Pearson相关性分析显示,癌灶组织miR-204-5p表达量与KMT2D表达量呈负相关(r=-0.602,P<0.05);胃癌组织miR-204-5p相对表达量在高、中、低分化中分别为 2.08±0.41、1.79±0.47、1.67±0.43(F=7.334,P<0.05),Ⅰ 和 Ⅱ、Ⅲ 和 Ⅳ 期中分别为 1.92±0.46、1.72±0.49(t=2.306,P<0.05),有、无淋巴结转移者中分别为 1.74±0.45、1.98±0.44(t=2.923,P<0.05);KMT2D 相对表达量在高、中、低分化中分别为 2.07±0.49、2.28±0.55、2.42±0.41(F=4.346,P<0.05),Ⅰ 和 Ⅱ、Ⅲ 和 Ⅳ期中分别为 2.14±0.52、2.38±0.60(t=2.347,P<0.05);miR-204-5p 高表达组 3 年生存率为 82.26%,高于 miR-204-5p 低表达组(62.07%,x2=6.126,P<0.05);KMT2D高表达组3年生存率为61.40%,低于KMT2D低表达组(82.54%,x2=6.705,P<0.05);Cox 多因素分析显示,TNM 分期 Ⅲ和Ⅳ期(HH=2.837,95%CI=1.913~4.207,P<0.05)、中低分化(HH=1.679,95%CI=1.241~2.273,P<0.05)、有淋巴结转移(HH=2.156,95%CI=1.625~2.864,P<0.05)、miR-204-5p 低表达(HH=1.823,95%CI=1.352~2.456,P<0.05)、KMT2D 高表达(HH=1.746,95%CI=1.309~2.329,P<0.05)均为预后不良的独立危险因素;ROC曲线显示,miR-204-5p、KMT2D预测胃癌患者3年内死亡的最佳截断值分别为1.85、2.20,对应的ROC曲线下面积(AUC)分别为0.682、0.690,敏感度分别为84.80%、84.80%,特异度分别为51.70%、52.90%,两者联合预测AUC为0.717,敏感度为87.90%,特异度为50.60%.结论 miR-204-5p低表达和KMT2D高表达与胃癌患者的疾病分期、组织分化和不良预后密切相关,两者联合预测3年内死亡风险具有一定价值.
Relationship between microRNA-204-5p and histone lysine methyltransferase 2D in gastric cancer tissues and disease staging and prognosis
Objective To analyze the association between expressions of microRNA-204-5p(miR-204-5p)and histone lysine methyltransferase 2D(KMT2D)in gastric cancer tissues and disease staging and prognosis.Methods 120 patients with gastric cancer in Jiangsu Armed Police Corps Hospital from January 2018 to January 2021 were selected for this study.The expression levels of miR-204-5p and KMT2D in cancerous and adjacent non-cancerous tissues were measured and analyzed in relation to clinico-pathological characteristics.Based on the expression levels of miR-204-5p and KMT2D,patients were di-vided into high miR-204-5p expression group(62 cases)and low miR-204-5p expression group(58 cases),as well as high KMT2D expression group(57 cases)and low KMT2D expression group(63 cases).The prognostic outcomes between the high and low expression groups of miR-204-5p and KMT2D were compared,and the predictive efficiency was assessed using receiver operating characteristic(ROC)curve analysis.T test or one-way analysis of variance were used between groups.The statistical da-ta were expressed as example(%)and x2 test was used.Results The relative expression level of miR-204-5p in cancer tissues with(1.78±0.46)was lower than(2.02±0.53)in adjacent tissues(t=3.746,P<0.05)while the relative expression level of KMT2D with(2.31±0.59)was higher than(1.88±0.57)in adjacent tissues(t=5.742,P<0.05).Pearson correlation analysis revealed that the expression level of miR-204-5p in cancer tissues was negatively correlated with the expression level of KMT2D(r=-0.602,P<0.05).The relative expression levels of miR-204-5p in gastric cancer tissues were 2.08±0.41,1.79±0.47 and 1.67±0.43 in patients with high,middle and low differentiation de-grees(F=7.334,P<0.05),were 1.92±0.46 and 1.72±0.49 in patients with stage Ⅰ/Ⅱ and stageⅢ/Ⅳ(t=2.306,P<0.05),and were 1.74±0.45 and 1.98±0.44 in patients with and without lymph node metastasis(t=2.923,P<0.05).The relative expression levels of KMT2D were 2.07±0.49,2.28±0.55 and 2.42±0.41 in patients with high,middle and low differentiation degrees(F=4.346,P<0.05),and were were 2.14±0.52 and 2.38±0.60 in patients with stage Ⅰ/Ⅱ and stage Ⅲ/Ⅳ(t=2.347,P<0.05).The 3-year survival rate of miR-204-5p high expression group was 82.26%,which was higher than 62.07%of miR-204-5p low expression group(x2=6.126,P<0.05).The 3-year survival rate of KMT2D high expression group was 61.40%,which was lower than 82.54%of KMT2D low expres-sion group(x2=6.705,P<0.05).Cox multivariate analysis showed that TNM stage Ⅲ 和Ⅳ(HH=2.837,95%CI=1.913-4.207,P<0.05),low-to-moderate differentiation(HH=1.679,95%CI=1.241-2.273,P<0.05),lymph node metastasis(HH=2.156,95%CI=1.625-2.864,P<0.05),low expression of miR-204-5p(HH=1.823,95%CI=1.352-2.456,P<0.05)and high expression of KMT2D(HH=1.746,95%CI=1.309-2.329,P<0.05)were independent risk factors for poor prognosis(P<0.05).ROC curve analysis showed that the best cutoff values of miR-204-5p and KMT2D for predic-ting the death within 3 years in gastric cancer patients were 1.85 and 2.20,the corresponding areas under ROC curves(AUCs)were 0.682 and 0.690,the sensitivities were 84.80%and 84.80%,and the speci-ficities were 51.70%and 52.90%respectively.The AUC of combined prediction was 0.717,with sensi-tivity of 87.90%and specificity of 50.60%.Conclusion Low expression of miR-204-5p and high ex-pression of KMT2D are closely associated with the disease stage,tissue differentiation,and poor prognosis in gastric cancer patients.The combination of these two factors has certain value in predicting the risk of death within three years.

Gastric cancerMicroRNA-204-5plysine methyltransferase 2DDisease stagingPrognosis

傅文杰、陆森、李鹏飞、杜文强、聂玉松、汪超

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武警江苏总队医院普外科,扬州 225000

上海新华医院普外科,上海 200092

淮安市肿瘤医院全科医学科,淮安 223200

胃癌 微小RNA-204-5p 组蛋白赖氨酸甲基转移酶2D 疾病分期 预后

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(12)