AHNAK2尿蛋白表达作为膀胱癌检测的潜在生物标志物：一项初步研究。

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study.

作者信息

Komina Selim, Petrusevska Gordana, Jovanovic Rubens, Kunovska Slavica Kostadinova, Stavridis Sotir, Dohcev Saso, Saidi Skender, Topuzovska Sonja

机构信息

Ss. Cyril and Methodious University, Faculty of Medicine, Institute of Pathology, Skopje, North Macedonia.

Ss. Cyril and Methodious University, Faculty of Medicine, University Urology Clinic, Skopje, North Macedonia.

出版信息

Turk J Urol. 2022 Nov;48(6):423-430. doi: 10.5152/tud.2022.22132.

DOI:10.5152/tud.2022.22132

PMID:36416332

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9797797/

Abstract

OBJECTIVE

This study aimed to measure the AHNAK2 urinary levels in bladder cancer patients.

MATERIAL AND METHODS

This prospective case-control study enrolled 67 participants between January and March 2019 and were categorized into bladder cancer group (n=37), with histologically proven bladder can cer, and control group (n=30), with histologically verified benign lesions or with no bladder cancer indica tion during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surger y and an enzyme-linked immunosorbent assay was performed as per the manufacturer's protocol. Bladder malignancies were classified according to the World Health Organization Tumor Classification. Group's associations were evaluated with the Student t-test, Spearman's rank correlation, and Mann-Whitney U test, while receiver operating curve was plotted for assessing the test's performance.

RESULTS

Mean age of the bladder cancer group was 66.41 years (standard deviation=10.04, range=43-82 years) and the control group was 59.67 years (standard deviation=10.44, range=38-77 years). All bladder cancers were of the urothelial histotype, with the following pT distribution: pTa/papillary urothelial neoplasm of low malignant potential (n=19; 28.4%), Primary tumor (pT) in situ (n=4; 6%), pT1 (n=7; 10.4%), and pT≥2 (n=7; 10.48%). Mean AHNAK2 levels were higher in bladder cancer patients 49.08 pg/mL (standard deviation=114.91) compared to controls 5.28 pg/mL (standard devia tion=6.65), P < .05). Significant differences were noted between non-invasive bladder cancer (n=23; mean=7.14 pg/mL; standard deviation=7.26) and invasive bladder cancer (n=14; mean=117.99 pg/mL; standard deviation=168.08) and between non-muscle invasive bladder cancer (mean=23.19 pg/mL; standard deviation=66.93) and muscle-invasive bladder cancer (mean=160.05 pg/mL; standard devia tion=199.65) (P < .001). The result of the assays was given as follows: sensitivity: 64.19%, specificity: 66.67%, positive predictive value: 22.07%, negative predictive value: 92.37%, area under curve: 0.695, and 95% CI: 0.57-0.82.

CONCLUSION

AHNAK2 protein could be used as bladder cancer surveillance biomarker. The inclusion of AHNAK2 levels in stratification nomograms might reduce the number of unnecessary cystoscopies.

摘要

目的

本研究旨在测量膀胱癌患者尿液中AHNAK2的水平。

材料与方法

这项前瞻性病例对照研究于2019年1月至3月招募了67名参与者，分为膀胱癌组（n = 37），其膀胱癌经组织学证实，以及对照组（n = 30），其组织学证实为良性病变或随访期间无膀胱癌迹象。在膀胱镜检查/手术前的上午中段收集15 mL尿液样本，并按照制造商的方案进行酶联免疫吸附测定。膀胱恶性肿瘤根据世界卫生组织肿瘤分类进行分类。采用学生t检验、Spearman等级相关性分析和Mann-Whitney U检验评估组间关联，同时绘制受试者工作曲线以评估该检测的性能。

结果

膀胱癌组的平均年龄为66.41岁（标准差 = 10.04，范围 = 43 - 82岁），对照组为59.67岁（标准差 = 10.44，范围 = 38 - 77岁）。所有膀胱癌均为尿路上皮组织学类型，pT分布如下：pTa/低恶性潜能乳头状尿路上皮肿瘤（n = 19；28.4%），原位原发性肿瘤（pT）（n = 4；6%），pT1（n = 7；10.4%），以及pT≥2（n = 7；10.48%）。膀胱癌患者的平均AHNAK2水平为49.08 pg/mL（标准差 = 114.91），高于对照组的5.28 pg/mL（标准差 = 6.65），P < 0.05）。非侵袭性膀胱癌（n = 23；平均值 = 7.14 pg/mL；标准差 = 7.26）与侵袭性膀胱癌（n = 14；平均值 = 117.99 pg/mL；标准差 = 168.08）之间以及非肌肉侵袭性膀胱癌（平均值 = 23.19 pg/mL；标准差 = 66.93）与肌肉侵袭性膀胱癌（平均值 = 160.05 pg/mL；标准差 = 199.65）之间存在显著差异（P < 0.001）。检测结果如下：敏感性：64.19%，特异性：66.67%，阳性预测值：22.07%，阴性预测值：92.37%，曲线下面积：0.695，95%置信区间：0.57 - 0.82。