摘要
目的探讨行肺癌根治术患者Yes相关蛋白1(YAP1)、YTH结构域连接蛋白2(YTHDF2)、miRNA-888-3p(miR-888-3p)的表达情况,及其对患者近期预后的预测价值。方法选择2015年5月至2022年5月山西省肿瘤医院420例行肺癌根治术的肺癌患者,通过计算机产生随机数法以2∶1将其分为建模集(280例)、验证集(140例);选择手术切除的癌旁正常肺组织(距离癌组织边缘>5 cm)作为对照。采用蛋白质印迹法检测建模集癌组织、癌旁组织YAP1、YTHDF2蛋白相对表达量,实时荧光定量聚合酶链反应(qRT-PCR)检测miR-888-3p相对表达量。统计患者随访1年预后情况,建模集患者出现复发、转移或癌因性死亡为预后不良组,其余患者为预后良好组。比较两组患者YAP1蛋白、YTHDF2蛋白、miR-888-3p相对表达量及一般资料;采用Cox比例风险模型分析建模集肺癌根治术近期预后的影响因素;构建肺癌根治术近期预后的Nomogram预测模型并验证其效能。结果建模集癌组织、癌旁组织miR-888-3p相对表达量分别为0.49±0.08和0.16±0.05,差异有统计学意义(t=58.53,P<0.001);YAP1蛋白的相对表达量分别为0.48±0.06、0.12±0.03,差异有统计学意义(t=89.80,P<0.001);YTHDF2蛋白的相对表达量分别为0.23±0.04、0.59±0.07,差异有统计学意义(t=74.72,P<0.001)。建模集随访1年,32例失访,其余248例中81例(32.66%)预后不良(预后不良组),167例(67.34%)为预后良好组。与预后良好组比较,预后不良组癌组织YAP1蛋白、miR-888-3p相对表达量均升高(均P<0.05),YTHDF2蛋白相对表达量降低(P<0.05);预后不良组吸烟、冠心病、TNM分期Ⅲ~Ⅳ期、肿瘤长径≥5 cm、组织分化程度未/低分化的患者比例均高,体力状况(PS)评分升高,术后规律放化疗患者比例降低(均P<0.05)。多因素Cox回归分析结果显示,吸烟(HR=2.098,95%CI 1.143~3.852,P=0.009)、TNM分期(HR=2.421,95%CI 1.350~4.341,P=0.002)、肿瘤长径(HR=1.883,95%CI 1.036~3.424,P=0.011)、组织分化程度(HR=3.133,95%CI 1.590~6.173,P<0.001)、术后规律放化疗(HR=0.417,95%CI 0.219~0.797,P=0.003)、YAP1(HR=7.043,95%CI 2.842~17.452,P<0.001)、YTHDF2(HR=0.560,95%CI 0.418~0.752,P<0.001)、miR-888-3p(HR=4.100,95%CI 1.789~9.394,P<0.001)是肺癌根治术近期预后的独立影响因素。建立Nomogram预测模型,内部验证显示模型的一致性指数为0.822(95%CI 0.774~0.870);受试者工作特征曲线结果显示,Nomogram预测模型预测建模集肺癌根治术近期预后的灵敏度为97.5%(95%CI 86.8%~99.9%),特异度为82.4%(95%CI 73.0%~89.6%),曲线下面积(AUC)为0.943(95%CI 0.889~0.976);预测验证集肺癌根治术近期预后的灵敏度为91.5%(95%CI 81.3%~97.2%),特异度为81.5%(95%CI 71.3%~89.2%),AUC为0.922(95%CI 0.865~0.961)。结论YAP1、YTHDF2、miR-888-3p均是肺癌根治术近期预后的影响因素,据此构建的Nomogram预测模型对肺癌根治术近期预后具有良好的预测效能。
ObjectiveTo investigate the expressions of Yes-associated protein 1(YAP1),YTH domain-containing family protein 2(YTHDF2)and microRNA-888-3p(miR-888-3p)in patients undergoing radical resection for lung cancer,and their predictive value for short-term prognosis of patients.MethodsA total of 420 lung cancer patients who underwent radical resection for lung cancer in Shanxi Province Cancer Hospital from May 2015 to May 2022 were selected and divided into a modeling set(280 cases)and a validation set(140 cases)in a ratio of 2∶1 by using the computer-generated random number method.The paracancerous normal lung tissues removed by surgery(>5 cm from the edge of the cancer tissues)were used as the control.The relative expressions of YAP1 and YTHDF2 proteins in cancer tissues and paracancerous tissues of the modeling set was detected by Western blotting,and the relative expression of miR-888-3p was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The patients were followed up for 1 year to analyze the prognosis,and the patients in the modeling set who had recurrence,metastasis or cancer-caused death were considered as the poor prognosis group,and the rest of the patients were considered as the good prognosis group.The relative expressions of YAP1 protein,YTHDF2 protein,miR-888-3p and general information of the patients in the two groups were compared;the Cox proportional hazards model was used to analyze the influencing factors of the short-term prognosis of radical resection for lung cancer in the modeling set;a Nomogram prediction model was constructed for the short-term prognosis of radical resection for lung cancer,and its efficacy was verified.ResultsThe relative expression of miR-888-3p in the modeling set of cancer tissues and paracancerous tissues was 0.49±0.08 and 0.16±0.05,and the difference was statistically significant(t=58.53,P<0.001);the relative expression of YAP1 protein was 0.48±0.06 and 0.12±0.03,and the difference was statistically significant(t=89.80,P<0.001);the relative expression of YTHDF2 protein was 0.23±0.04 and 0.59±0.07,and the difference was statistically significant(t=74.72,P<0.001).After 1 year of follow-up in the modeling set,32 cases were lost,and 81(32.66%)of the remaining 248 cases had a poor prognosis(poor prognosis group),while 167 cases(67.34%)were in the good prognosis group.Compared with the good prognosis group,the relative expressions of YAP1 protein and miR-888-3p in cancer tissues was elevated in the poor prognosis group(both P<0.05),and the relative expression of YTHDF2 protein was decreased(P<0.05);the proportions of patients with smoking,coronary artery disease,TNM stageⅢ-Ⅳ,maximum tumor diameter≥5 cm,and undifferentiated/lowly differentiated tissues were high in the poor prognosis group,the physical status(PS)score was elevated,and the proportion of patients with regular postoperative radiotherapy was reduced(all P<0.05).The results of multivariate Cox regression analysis showed that the proportion of patients with smoking(HR=2.098,95%CI 1.143-3.852,P=0.009),TNM stage(HR=2.421,95%CI 1.350-4.341,P=0.002),maximum tumor diameter(HR=1.883,95%CI 1.036-3.424,P=0.011),degree of tissue differentiation(HR=3.133,95%CI 1.590-6.173,P<0.001),regular postoperative radiotherapy(HR=0.417,95%CI 0.219-0.797,P=0.003),YAP1(HR=7.043,95%CI 2.842-17.452,P<0.001),YTHDF2(HR=0.560,95%CI 0.418-0.752,P<0.001),and miR-888-3p(HR=4.100,95%CI 1.789-9.394,P<0.001)were the independent influencing factors for the short-term prognosis of radical resection for lung cancer.A Nomogram prediction model was constructed,and internal validation showed that the consistency index of the model was 0.822(95%CI 0.774-0.870);the result of receiver operator characteristic curve showed that the sensitivity of the Nomogram prediction model for predicting the short-term prognosis of radical resection for lung cancer in the modeling set was 97.5%(95%CI 86.8%-99.9%),and the specificity was 82.4%(95%CI 73.0%-89.6%),and the area under the curve(AUC)was 0.943(95%CI 0.889-0.976);the sensitivity of predicting the short-term prognosis of radical resection for lung cancer in the validation set was 91.53%(95%CI 81.3%-97.2%),and the specificity was 81.5%(95%CI 71.3%-89.2%),and the AUC was 0.922(95%CI 0.865-0.961).ConclusionsYAP1,YTHDF2 and miR-888-3p are all influencing factors for short-term prognosis of radical resection for lung cancer,and the Nomogram prediction model constructed based on these factors has good predictive efficacy for the short-term prognosis of radical resection for lung cancer.
作者
郑康
薄云峰
刘冠华
Zheng Kang;Bo Yunfeng;Liu Guanhua(Department of Thoracic Surgery,Shanxi Province Cancer Hospital,Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences,Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China;Department of Pathology,Shanxi Province Cancer Hospital,Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences,Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China)
出处
《肿瘤研究与临床》
CAS
2023年第9期646-652,共7页
Cancer Research and Clinic
关键词
肺肿瘤
预后
影响因素
预测模型
Lung neoplasms
Prognosis
Influencing factors
Prediction model
作者简介
通信作者:郑康,Email:13503513792@163.com。
