Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Pulau Pinang, Malaysia.
School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, Malaysia.
Sci Rep. 2021 Mar 24;11(1):6765. doi: 10.1038/s41598-021-85993-x.
Distinguishing bladder urothelial carcinomas from prostate adenocarcinomas for poorly differentiated carcinomas derived from the bladder neck entails the use of a panel of lineage markers to help make this distinction. Publicly available The Cancer Genome Atlas (TCGA) gene expression data provides an avenue to examine utilities of these markers. This study aimed to verify expressions of urothelial and prostate lineage markers in the respective carcinomas and to seek the relative importance of these markers in making this distinction. Gene expressions of these markers were downloaded from TCGA Pan-Cancer database for bladder and prostate carcinomas. Differential gene expressions of these markers were analyzed. Standard linear discriminant analyses were applied to establish the relative importance of these markers in lineage determination and to construct the model best in making the distinction. This study shows that all urothelial lineage genes except for the gene for uroplakin III were significantly expressed in bladder urothelial carcinomas (p < 0.001). In descending order of importance to distinguish from prostate adenocarcinomas, genes for uroplakin II, S100P, GATA3 and thrombomodulin had high discriminant loadings (> 0.3). All prostate lineage genes were significantly expressed in prostate adenocarcinomas(p < 0.001). In descending order of importance to distinguish from bladder urothelial carcinomas, genes for NKX3.1, prostate specific antigen (PSA), prostate-specific acid phosphatase, prostein, and prostate-specific membrane antigen had high discriminant loadings (> 0.3). Combination of gene expressions for uroplakin II, S100P, NKX3.1 and PSA approached 100% accuracy in tumor classification both in the training and validation sets. Mining gene expression data, a combination of four lineage markers helps distinguish between bladder urothelial carcinomas and prostate adenocarcinomas.
区分来源于膀胱颈部的低分化膀胱癌和前列腺腺癌需要使用一系列谱系标志物来帮助做出这种区分。公开的癌症基因组图谱（TCGA）基因表达数据提供了一种检查这些标志物效用的途径。本研究旨在验证各自癌组织中尿路上皮和前列腺谱系标志物的表达，并寻求这些标志物在做出这种区分中的相对重要性。从 TCGA 泛癌数据库下载这些标志物的基因表达数据。分析这些标志物的差异基因表达。应用标准线性判别分析来确定这些标志物在谱系确定中的相对重要性，并构建最佳的模型来进行区分。本研究表明，除了 uroplakin III 基因外，所有尿路上皮谱系基因在膀胱尿路上皮癌中均有显著表达（p<0.001）。按区分前列腺腺癌的重要性降序排列，uroplakin II、S100P、GATA3 和血栓调节蛋白的基因具有较高的判别负荷（>0.3）。所有前列腺谱系基因在前列腺腺癌中均有显著表达（p<0.001）。按区分膀胱尿路上皮癌的重要性降序排列，NKX3.1、前列腺特异性抗原（PSA）、前列腺特异性酸性磷酸酶、prostein 和前列腺特异性膜抗原的基因具有较高的判别负荷（>0.3）。uroplakin II、S100P、NKX3.1 和 PSA 基因表达的组合在训练集和验证集中的肿瘤分类中均达到了接近 100%的准确率。挖掘基因表达数据，结合四个谱系标志物有助于区分膀胱尿路上皮癌和前列腺腺癌。
