非肌层浸润性膀胱癌组织中PKM2和ALYREF表达及与预后预测价值研究  

Expression of PKM2 and ALYREF in Non-muscular Invasive Bladder Cancer and Their Prognostic Value

作　　者：朱军 沈欣 曹冬 ZHU Jun;SHEN Xin;CAO Dong(Department of Urology Surgery,Jingjiang City Hospital of Traditional Chinese Medicine Affiliated Hospital of Hanlin College of Nanjing University of Chinese Medicine,Jiangsu Jingjiang 214500,China)

机构地区：[1]江苏省靖江市中医院/南京中医药大学翰林学院附属医院泌尿外科,江苏靖江214500

出　　处：《现代检验医学杂志》2023年第5期110-114,154,共6页Journal of Modern Laboratory Medicine

基　　金：江苏省卫生健康委医学科研立项项目(课题编号:BJ20021):PKM2与ALYREF非肌层浸润性膀胱癌组织中表达及预后的相关性研究。

摘　　要：目的 研究非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)组织中丙酮酸激酶M2亚型(pyruvate kinase M2 subtype,PKM2),RNA结合蛋白Aly/REF输出因子(Aly/REF export factor,ALYREF)表达及预后意义。方法 选取自2017年2月~2020年2月期间南京中医药大学翰林学院附属医院收治的84例NMIBC患者为研究对象。免疫组织化学检测NMIBC和膀胱正常黏膜组织中PKM2和ALYREF蛋白表达。Spearman秩相关分析膀胱癌组织中PKM2和ALYREF蛋白表达相关性。Kaplan-Meier生存曲线分析(Log-Rank检验)PKM2和ALYREF蛋白对无进展生存(progress free survive, PFS)预后的影响。COX比例风险模型分析影响NMIBC患者PFS预后的因素。结果 NMIBC组织中PKM2(71.43%),ALYREF(73.81%)蛋白阳性率高于膀胱正常黏膜组织(11.90%,10.71%),差异具有统计学意义(χ^(2)=61.225,68.522,均P <0.05)。T1期、高级别NMIBC癌组织中PKM2(88.37%,90.32%),ALYREF(80.05%,93.55%)蛋白阳性率分别高于Ta/Tis期(53.66%,60.38%)、低级别癌组织(60.98%,62.26%),差异具有统计学意义(χ^(2)=12.393,8.594;6.524,9.903,均P <0.05)。PKM2阳性组和阴性组患者的三年总体PFS分别为48.33%(29/60),87.50%(21/24),PKM2阳性组患者三年累积PFS显著低于PKM2阴性组患者(Log-Rank testχ^(2)=10.040,P=0.002);ALYREF阳性组和阴性组三年总体PFS分别为48.39%(30/62),90.91%(20/22),ALYREF阳性组患者三年累积PFS显著低于阴性组患者(Log-Rank test χ^(2)=11.110,P=0.001)。肿瘤TNM分期T1期(HR=1.614,95%CI:1.227~2.214)、高级别(HR=1.921,95%CI:1.324~2.788),PKM2阳性(HR=1.837,95%CI:1.229~2.745),ALYREF阳性(HR=1.744,95%CI:1.245~2.443)是影响NMIBC患者PFS预后的独立危险因素。结论 NMIBC中PKM2和ALYREF表达升高,两者表达呈正相关,是影响NMIBC患者预后的独立因素。Objective To study the expression of pyruvate kinase M2 subtype(PKM2),RNA binding protein Aly/REF output factor(ALYREF)and their prognostic significance in non-muscle invasive bladder cancer(NMIBC).Methods 84 patients with NMIBC admitted to Nanjing University of Chinese Medicine Hanlin College from February 2017 to February 2020 were selected as the study subjects.Immunohistochemistry was used to detect the expression of PKM2 and ALYREF protein in NMIBC and normal bladder mucosa tissues.Spearman rank correlation analysis of PKM2 and ALYREF protein expression in bladder cancer tissue.Kaplan-Meier survival curve analysis(Log-Rank test)was used to analyze the effect of PKM2 and ALYREF protein on the prognosis of progression-free survival(PFS).COX proportional risk model was used to analyze the factors affecting the prognosis of PFS in patients with NMIBC.Results The positive rate of PKM2(71.43%)and ALYREF(73.81%)protein in NMIBC bladder cancer tissue was higher than that in normal bladder mucosa tissue(11.90%,10.71%),with statistical significance(χ^(2)=61.225,68.522,all P<0.05).The positive rates of PKM2(88.37%,90.32%)and ALYREF(80.05%,93.55%)protein in T1 and high-grade NMIBC cancer tissues were higher than those in Ta/Tis(53.66%,60.38%)and low-grade cancer tissues(60.98%,62.26%),and the differences were statistically significant(χ^(2)=12.393,8.594;6.824,9.903,all P<0.05).The 3-year total PFS of PKM2 positive group and negative group were 48.33%(29/60)and 87.50%(21/24)respectively.The cumulative PFS of patients in the PKM2 positive group in 3 years was significantly lower than that of patients in the PKM2 negative group(Log-Rank testχ^(2)=10.040,P=0.002).The overall PFS of ALYREF positive group and negative group in 3 years were 48.39%(30/62)and 90.91%(20/22)respectively.The cumulative PFS of patients in the ALYREF positive group in 3 years was significantly lower than that of patients in the negative group(Log-Rank testχ^(2)=11.110,P=0.001).Tumor TNM stage T1(HR=1.614,95%CI:1.227~2.214),high grade(HR=1.921

关 键 词：非肌层浸润膀胱癌 丙酮酸激酶M2亚型 RNA结合蛋白Aly/REF输出因子 

分 类 号：R737.14[医药卫生—肿瘤] R730.43[医药卫生—临床医学]