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Joint analysis of WES and RNA-Seq identify signature genes related to metastasis in prostate cancer |
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| Authors: | Chongjun Xiang Yue Li Wenting Wang Huiying Tao Ning Liang Shuang Wu Tianxi Yu Xin Cui Yaqi Xie Hongwei Zuo Chunhua Lin Fuyi Xu |
| Institution: | 1. The 2nd Medical College of Binzhou Medical University, Yantai, China
Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Data curation (supporting), Formal analysis (lead), Software (equal), Visualization (equal), Writing - original draft (equal);2. The 2nd Medical College of Binzhou Medical University, Yantai, China Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Formal analysis (equal), Writing - original draft (equal);3. Department of Central Laboratory, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Data curation (lead);4. The 2nd Medical College of Binzhou Medical University, Yantai, China Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Software (equal);5. Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China School of Clinical Medicine, Weifang Medical University, Weifang, China Contribution: Visualization (equal);6. Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Resources (equal);7. Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China School of Clinical Medicine, Weifang Medical University, Weifang, China Contribution: Resources (equal);8. The 2nd Medical College of Binzhou Medical University, Yantai, China Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China Contribution: Resources (equal);9. Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China;10. Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, School of Pharmacy, Binzhou Medical University, Yantai, China |
| Abstract: | Prostate cancer (PCa) has a certain degree of heritability, and metastasis occurs as cancer progresses. However, its underlying mechanism remains largely unknown. We sequenced four cases of cancer without metastasis, four metastatic cancer, and four benign hyperplasia tissues as controls. A total of 1839 damaging mutations were identified. Pathway analysis, gene clustering, and weighted gene co-expression network analysis were employed to find characteristics associated with metastasis. Chr19 had the most mutation density and 1p36 had the highest mutation frequency across the genome. These mutations occurred in 1630 genes, including the most frequently mutated genes TTN and PLEC, and dozens of metastasis-related genes, such as FOXA1, NCOA1, CD34, and BRCA2. Ras signalling and arachidonic acid metabolism were uniquely enriched in metastatic cancer. Gene programmes 10 and 11 showed the signatures indicating the occurrence of metastasis better. A module (135 genes) was specifically associated with metastasis. Of them, 67.41% reoccurred in program 10, with 26 genes further retained as the signature genes related to PCa metastasis, including AGR3, RAPH1, SOX14, DPEP1, and UBL4A. Our study provides new molecular perspectives on PCa metastasis. The signature genes and pathways could be served as potential therapeutic targets for metastasis or cancer progression. |
| Keywords: | gene expression metastasis prostate cancer RNA-Seq WES |