National Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
Clinical Laboratory Department, College of Applied Medical Sciences, Shaqra University, KSA, Al dawadmi, Saudi Arabia.
Mol Carcinog. 2019 Jun;58(6):862-874. doi: 10.1002/mc.22975. Epub 2019 Jan 31.
A considerable number of deposited variants has provided new possibilities for knowledge discovery in different types of prostate cancer. Here, we analyzed variants located on 3'UTR, 5'UTR, CDs, Intergenic, and Intronic regions in castration-resistant prostate cancer (8496 variants), familial prostate cancer (3241 variants), metastatic castration-resistant prostate cancer (3693 variants), and prostate cancer (16599 variants). Chromosome regions 10p15-p14 and 2p13 were highly enriched (P < 0.00001) for variants located in 3'UTR, 5'UTR, CDs, intergenic, and intronic regions in castration-resistant prostate cancer. In contrast, 10p15-p14, 10q23.3, 12q13.11, 13q12.3, 1q25, and 8p22 regions were enriched (P < 0.001) in familial prostate cancer. In metastatic castration-resistant prostate cancer, 10p15-p14, 10q23.3, 11q22-q23, 14q21.1, and 14q32.13 were highly variant regions (P < 0.001). Chromosome 2 and chromosome 1 hosted many enriched variant regions. AKR1C3, BRCA1, BRCA2, CHGA, CYP19A1, HOXB13, KLK3, and PTEN contained the highest number of 3'UTR, 5'UTR, CDs, Intergenic, and Intronic variants. Network analysis showed that these genes are upstream of important functions including prostate gland development, tumor recurrence, prostate cancer-specific survival, tumor progression, cancer mortality, long-term survival, cancer recurrence, angiogenesis, and AR. Interestingly, all of EGFR, JAK2, NR3C1, PDZD2, and SEMA3C genes had single nucleotide polymorphisms (SNP) in castration-resistant prostate cancer, consistent with high selection pressure on these genes during drug treatment and consequent resistance. High occurrence of variants in 3'UTRs suggests the importance of regulatory variants in different types of prostate cancer; an area that has been neglected compared with coding variants. This study provides a comprehensive overview of genomic regions contributing to different types of prostate cancer.
大量的已发现变体为不同类型前列腺癌的知识发现提供了新的可能性。在这里，我们分析了在去势抵抗性前列腺癌（8496 个变体）、家族性前列腺癌（3241 个变体）、转移性去势抵抗性前列腺癌（3693 个变体）和前列腺癌（16599 个变体）中位于 3'UTR、5'UTR、CDs、基因间和内含子区域的变体。染色体区域 10p15-p14 和 2p13 在去势抵抗性前列腺癌中位于 3'UTR、5'UTR、CDs、基因间和内含子区域的变体高度富集（P<0.00001）。相比之下，10p15-p14、10q23.3、12q13.11、13q12.3、1q25 和 8p22 区域在家族性前列腺癌中富集（P<0.001）。在转移性去势抵抗性前列腺癌中，10p15-p14、10q23.3、11q22-q23、14q21.1 和 14q32.13 是高度变体区域（P<0.001）。染色体 2 和染色体 1 包含许多富集的变体区域。AKR1C3、BRCA1、BRCA2、CHGA、CYP19A1、HOXB13、KLK3 和 PTEN 包含最多的 3'UTR、5'UTR、CDs、基因间和内含子变体。网络分析表明，这些基因是前列腺发育、肿瘤复发、前列腺癌特异性生存、肿瘤进展、癌症死亡率、长期生存、癌症复发、血管生成和 AR 等重要功能的上游基因。有趣的是，所有 EGFR、JAK2、NR3C1、PDZD2 和 SEMA3C 基因在去势抵抗性前列腺癌中都有单核苷酸多态性（SNP），这表明在药物治疗过程中这些基因受到了强烈的选择压力，从而导致了耐药性。3'UTR 中变体的高发生率表明调节变体在不同类型前列腺癌中的重要性；与编码变体相比，这一领域一直被忽视。本研究提供了一个全面的概述，说明了导致不同类型前列腺癌的基因组区域。
