Appunni Sandeep, Anand Vivek, Khandelwal Madhuram, Seth Amlesh, Mathur Sandeep, Sharma Alpana
1 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
2 Department of Urology, All India Institute of Medical Sciences, New Delhi, India.
Tumour Biol. 2017 May;39(5):1010428317699112. doi: 10.1177/1010428317699112.
Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.
富含亮氨酸的小分子蛋白聚糖是细胞外基质的组成成分，可调节肿瘤转化。在富含亮氨酸的小分子蛋白聚糖中，核心蛋白聚糖、双糖链蛋白聚糖和纤连蛋白聚糖是最常涉及的标志物，并且它们在各种恶性肿瘤中的表达已得到充分研究。在这项新研究中，我们共同评估了这三种分子在膀胱尿路上皮癌中的表达。招募了30例确诊未治疗的膀胱癌患者、30例血液健康对照者和30例相邻非肿瘤组织对照者。采集了所有受试者的血液，并从患者身上获取肿瘤/相邻正常组织。通过酶联免疫吸附测定法估计循环水平，通过定量聚合酶链反应估计相对信使核糖核酸表达，通过免疫组织化学和蛋白质印迹法估计蛋白质表达。与对照相比，患者体内双糖链蛋白聚糖（p = 0.0038）和纤连蛋白聚糖（p < 0.0001）的循环水平显著升高，而核心蛋白聚糖（p < 0.0001）的循环水平显著降低。免疫组织化学和蛋白质印迹法检测的蛋白质表达显示，膀胱尿路上皮癌中纤连蛋白聚糖和双糖链蛋白聚糖表达升高，而核心蛋白聚糖表达降低。对组织标本信使核糖核酸表达进行的定量聚合酶链反应显示，膀胱尿路上皮癌中双糖链蛋白聚糖（p = 0.0008）和纤连蛋白聚糖（p = 0.01）表达显著升高，而核心蛋白聚糖（p < 0.0001）表达降低。在所有分子中，受试者工作特征曲线显示，血清纤连蛋白聚糖的0.207 ng/ml临界值提供了最佳敏感性（90.0%）和特异性（90.0%）。观察到膀胱尿路上皮癌中基质富含亮氨酸的小分子蛋白聚糖有显著改变。在具有最高最佳敏感性和特异性临界值的膀胱癌患者中，纤连蛋白聚糖的高表达表明其作为潜在非侵入性标志物对膀胱癌早期检测的重要性，有待在大型患者队列中进一步验证。
