Shin Ye Ji, Yun Jae Won, Kim Hong Sook
Department of Biological Sciences, Sungkyunkwan University, Suwon 19419, Korea.
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Korea.
Biomedicines. 2022 Oct 20;10(10):2650. doi: 10.3390/biomedicines10102650.
Gene fusion between androgen receptor (AR) response genes and E26 transformation-specific (ETS) family members increases the gene expression of ETS family members, and promotes tumorigenesis in prostate cancer. However, the molecular features of fusion in prostate cancer are not fully understood, and drugs targeting fusion have not been developed. To examine key cellular signaling pathways and explore therapeutic targets and drugs for -fusion-positive prostate cancer, we analyzed RNA sequencing data and clinical information for prostate cancer. The -fusion-positive group was selected through prior study and analysis comparing -fusion-positive and -negative groups was conducted using a Pearson correlation test. We obtained 393 genes correlated with expression. Pathway analysis was performed using over-representation analysis (ORA), and six cancer-specific molecular signaling pathways (the irinotecan pathway, metabolism, androgen receptor signaling, interferon signaling, MAPK/NF-kB signaling, and the tamoxifen pathway) were altered in the -fusion-positive group. Furthermore, a gene-drug database was used to find an actionable drug and therapeutic target for the -fusion-positive group. Here, we have identified significantly altered genes and oncogenic signaling pathways in -fusion-positive prostate cancer, and we suggest therapeutic targets and potential drugs for -fusion-positive prostate patients.
雄激素受体（AR）反应基因与E26转化特异性（ETS）家族成员之间的基因融合会增加ETS家族成员的基因表达，并促进前列腺癌的肿瘤发生。然而，前列腺癌中基因融合的分子特征尚未完全了解，且针对基因融合的药物尚未开发出来。为了研究关键细胞信号通路，并探索针对基因融合阳性前列腺癌的治疗靶点和药物，我们分析了前列腺癌的RNA测序数据和临床信息。通过先前的研究选择基因融合阳性组，并使用Pearson相关检验对基因融合阳性组和阴性组进行比较分析。我们获得了393个与基因表达相关的基因。使用过表达分析（ORA）进行通路分析，结果显示基因融合阳性组中有六个癌症特异性分子信号通路（伊立替康通路、代谢、雄激素受体信号通路、干扰素信号通路、MAPK/NF-kB信号通路和他莫昔芬通路）发生了改变。此外，利用基因-药物数据库为基因融合阳性组寻找可操作的药物和治疗靶点。在此，我们已经确定了基因融合阳性前列腺癌中显著改变的基因和致癌信号通路，并为基因融合阳性前列腺癌患者提出了治疗靶点和潜在药物。
