详情页 - 河北医科大学第四医院机构库

当前位置：首页 > 详情页

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence.

14| 导出 | 链接全文 |

文献详情

资源类型：

WOS体系：

Pubmed体系：

收录情况： ◇ SCIE

作者：

机构： [1]Department of Gastroenterology, Xiangya Hospital, Central South University, Changsa, Hunan, China [2]Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada [3]Father Sean O’Sullivan Research Institute, Hamilton, Canada [4]The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Canada [5]Department of Nephrology, The First Affiliated Hospital of Nanchang University, Jiangxi, China [6]Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA [7]Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang City, China [8]The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, China [9]Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, Ontario, Canada

出处：

DOI：

ISSN：

关键词： biomarkers MUC1 prostate cancer prostate cancer recurrence

摘要：

We report here numerous novel genes and multiple new signatures which robustly predict prostate cancer (PC) recurrence. We extracted 696 differentially expressed genes relative to a reported PC signature from the TCGA dataset (n = 492) and built a 15-gene signature (SigMuc1NW) using Elastic-net with 10-fold cross-validation through analyzing their expressions at 1.5 standard deviation/SD below and 2 SD above a population mean. SigMuc1NW predicts biochemical recurrence (BCR) following surgery with 56.4% sensitivity, 72.6% specificity, and 63.24 median months disease free (MMDF) (P = 1.12e-12). The prediction accuracy is improved with the use of SigMuc1NW's cutpoint (P = 3e-15) and is further enhanced (sensitivity 67%, specificity 75.7%, MMDF 45.2, P = 0) when all 15 genes were analyzed through their cutpoints instead of their SDs. These genes individually associate with BCR using either SD or cutpoint as the cutoff points. Eight of 15 genes are individual risk factors after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. Eleven of 15 genes are novel to PC. SigMuc1NW discriminates BCR with time-dependent AUC (tAUC) values of 76.6% at 11.5 months (76.6%-11.5 m), 73.8%-22.3 m, 78.5%-32.1 m, and 76.4%-48.4 m. SigMuc1NW is correlated with adverse features of PC, high Gleason scores (odds ratio/OR 1.48, P < 2e-16), and advanced tumor stages (OR 1.33, P = 4.37e-13). SigMuc1NW remains an independent risk factor of BCR (HR 2.44, 95% CI 1.53-3.87, P = 1.62e-4) after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. In an independent PC (MSKCC) cohort (n = 140), these 15 genes were altered in PC vs normal tissue, metastatic PCs vs primary PCs, and recurrent PCs vs nonrecurrent PCs. Importantly, a 10-gene subsignature SigMuc1NW1 predicts BCR in MSKCC (P = 3.11e-15) and TCGA (P = 3.13e-12); SigMuc1NW1 discriminates BCR at 18.4 m with tAUC as 82.5%. Collectively, our analyses support SigMuc1NW as a novel and robust signature in predicting BCR of PC. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

基金：

语种：

被引次数：

WOS：

PubmedID：

中科院分区：

出版当年[2018]版：

大类 | 2 区医学

小类 | 2 区肿瘤学

最新[2025]版：

大类 | 2 区医学

小类 | 3 区肿瘤学

JCR分区：

出版当年[2018]版：

Q1 ONCOLOGY

最新[2023]版：

Q1 ONCOLOGY

影响因子： 5 最新[2023版] 6.5 最新五年平均 5.962 出版当年[2018版] 5.497 出版当年五年平均 5.264 出版前一年[2017版] 6.574 出版后一年[2019版]

第一作者：

第一作者机构： [1]Department of Gastroenterology, Xiangya Hospital, Central South University, Changsa, Hunan, China [2]Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada [3]Father Sean O’Sullivan Research Institute, Hamilton, Canada [4]The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Canada

共同第一作者：

通讯作者：

通讯机构： [2]Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada [3]Father Sean O’Sullivan Research Institute, Hamilton, Canada [4]The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Canada [9]Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, Ontario, Canada [*1]St. Joseph’s Hospital, T3310, 50 Charlton Ave East, Hamilton L8N 4A6, Ontario, Canada [*2]Division of Medical Oncology, Department of Oncology, McMaster University, 699 Concession Street, Hamilton L8V 5C2, Ontario, Canada

推荐引用方式(GB/T 7714)：

APA：

MLA：

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence.

文献详情

相关文献