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A 12-gene panel in estimating hormone-treatment responses of castration-resistant prostate cancer patients generated using a combined analysis of bulk and single-cell sequencing data

Dataset

  • Juanlan Huang (Creator)
  • Dale Liu (Creator)
  • Jun Li (Creator)
  • Jing Xu (Creator)
  • Shaowei Dong (Creator)
  • Hao ZhangDepartment of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China, Chinese Academy of Sciences, Pudong Medical Center, Heilongjiang Provincial Hospital, Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, China;, Beijing Anzhen Hospital, Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences, Guangdong Pharmaceutical University, China agricultural University, First Affiliated Hospital of Harbin Medical University, Guangdong University of Petrochemical Technology, Jiangsu Province Hospital, Dalian University of Technology, University of Arizona, Nanchang University, Huazhong University of Science and Technology, McGill University, Shandong University, Chongqing Medical University, Shanghai Jiao Tong University, University of Chinese Academy of Sciences, South China University of Technology, Shanghai Stomatological Hospital, Yangzhou University, Jiangsu University of Science and Technology, Cornell University, Hunan Agricultural University, University of Victoria, Second Affiliated Hospital of Harbin Medical University, Jilin University, Nanyang Technological University, Changhai Hospital, Zhongnan Hospital of Wuhan University, Ruian People's Hospital, Nanjing Agricultural University, Yunnan Academy of Agricultural Sciences, Northwestern Polytechnical University Xian, Hubei Academy of Agricultural Sciences, Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Fudan University, Ocean University of China, Harvard University, Ruijin Hospital, Jinan University, Sichuan University, Second Affiliated Hospital of Nanjing Medical University, Jiangnan University, Shanghai Children's Medical Center, Urology Department The Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University Qingdao Shandong China, Zhejiang University, Nanjing Medical University, Wenzhou Medical University, Chinese Academy of Medical Sciences & Peking Union Medical College, Henan Normal University (Creator)

Description

Castration-resistant prostate cancer (CRPC) represents one type of advanced prostate cancer (PCa) with a median survival time of 1–2 years. Currently, there is a lack of reliable gene panels in predicting hormone treatment (HT) responses due to limited knowledge of CRPC-specific tumor-microenvironment (TME) characteristics. In this study, we first screened for up-regulated genes in CRPC samples using bulk-sequencing data retrieved from TCGA online database, and further investigated the expression status of these genes in four sets of downloaded single-cell RNA sequencing (scRNAseq) data: GSE117403 containing 16 normal human prostate samples; GSE141445 containing 13 PCa samples; GSE176031 containing 11 PCa samples and GSE137829 containing 6 CRPC samples. We identified a series of CRPC-specific TME characteristics including an enriched number of PEG10+ neuroendocrine cells, elevated expression of PPIB/CCDC74A/GAPDH/AR genes in tumor cells, increased expression of FAP/TGFB1 in cancer-associated fibroblasts (CAFs), suppressed immune environment featured by enhanced M2 macrophage polarization, T cell exhaustion and increased number of regulatory B cells. We further established a 12-gene panel using these characteristics and showed that this panel could separate CRPC samples from PCa samples (AUC of 0.78), and CRPC patients with higher panel scores tended to have treatment failure or progression (R = −0.47, p = 0.019). Based on these unique TME characteristics of CRPC, we established a prediction tool for estimating the duration of HT responses in PCa treatment. Our results suggest mechanisms by which prostate cancer becomes castrate resistant. Further study of PEG10 (and/or others) to evaluate therapeutic efficacy should be considered. Increased number of PEG10+ neuroendocrine cells is associated with recurrence of HT PCa patients A 12-gene panel could be used to predict duration of HT responses in PCa treatment
Date made available2023
PublisherTaylor & Francis

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