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全面分析鉴定前列腺腺癌生化复发的 Wnt 配体基因家族,并构建列线图。

Comprehensive Analysis Identifying Wnt Ligands Gene Family for Biochemical Recurrence in Prostate Adenocarcinoma and Construction of a Nomogram.

机构信息

Department of Urology, Peking University Fifth School of Clinical Medicine, Beijing, China.

Department of Urology, Beijing Hospital, National Center of Gerontology, Beijing, China.

出版信息

J Comput Biol. 2020 Dec;27(12):1656-1667. doi: 10.1089/cmb.2019.0397. Epub 2020 Apr 16.

Abstract

There is little research to explore the relationship between Wnt ligands gene family and biochemical recurrence of prostate adenocarcinoma. The purpose of this study was to systematically evaluate the role of Wnt ligands gene family in biochemical recurrence in prostate adenocarcinoma. RNA-seq transcriptome data and clinicopathological data of 489 prostate adenocarcinoma tissues and 51 nontumor tissues were obtained from The Cancer Genome Atlas. We developed a risk score model with the least absolute shrinkage and selection operator Cox regression algorithm. We used the X-tile program to derive the best threshold for risk scores, dividing patients into high-, intermediate-, and low-risk groups. Gene set enrichment analysis (GSEA) was performed. Nomogram was constructed based on the risk score and clinical features. The risk score = (0.192 × expression level of Wnt9A) + (0.732 × expression level of Wnt8B) + (0.051 × expression level of Wnt7B) + (-0.320 × expression level of Wnt3A). The risk score was an independent prognostic factor, with a hazard ratio of 1.298 (95% confidence interval: 1.046-1.612;  = 0.018). GSEA revealed that the Kyoto Encyclopedia of Genes and Genomes pathway of the four selected genes was closely related to malignancy-related biological processes. Nomogram was constructed based on the risk score and clinical features. The C index was 0.719, and the calibration curve showed that the nomogram performed well. In general, we comprehensively evaluated the association between Wnt ligands gene family and biochemical recurrence of prostate cancer. We developed a risk score model based on messenger RNA expression levels of several selected Wnt ligand family genes (Wnt3A, Wnt7B, Wnt8B, and Wnt9A), which was significantly associated with biochemical recurrence of prostate cancer. Our results might be helpful for future molecular studies focusing on the biochemical recurrence of prostate cancer.

摘要

关于 Wnt 配体基因家族与前列腺腺癌生化复发的关系,研究甚少。本研究旨在系统评估 Wnt 配体基因家族在前列腺腺癌生化复发中的作用。我们从癌症基因组图谱中获取了 489 例前列腺腺癌组织和 51 例非肿瘤组织的 RNA-seq 转录组数据和临床病理数据。我们使用最小绝对收缩和选择算子 Cox 回归算法开发了一个风险评分模型。我们使用 X-tile 程序确定风险评分的最佳阈值,将患者分为高风险、中风险和低风险组。进行基因集富集分析(GSEA)。基于风险评分和临床特征构建列线图。风险评分=(0.192×Wnt9A 的表达水平)+(0.732×Wnt8B 的表达水平)+(0.051×Wnt7B 的表达水平)+(-0.320×Wnt3A 的表达水平)。风险评分是一个独立的预后因素,危险比为 1.298(95%置信区间:1.046-1.612;=0.018)。GSEA 显示,四个选定基因的京都基因与基因组百科全书通路与恶性相关的生物学过程密切相关。基于风险评分和临床特征构建列线图。C 指数为 0.719,校准曲线显示列线图表现良好。总之,我们综合评估了 Wnt 配体基因家族与前列腺癌生化复发的关系。我们基于几个选定的 Wnt 配体家族基因(Wnt3A、Wnt7B、Wnt8B 和 Wnt9A)的信使 RNA 表达水平开发了一个风险评分模型,该模型与前列腺癌的生化复发显著相关。我们的研究结果可能有助于未来关注前列腺癌生化复发的分子研究。

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