AUTHOR=Li Yuezheng , Wang Haoyu , Pan Yang , Wang Shangren , Zhang Zhexin , Zhou Hang , Xu Mingming , Liu Xiaoqiang 

TITLE=Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1125299

DOI=10.3389/fendo.2023.1125299

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance.</p></sec><sec><title>Methods</title><p>The data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups.</p></sec><sec><title>Results</title><p>Two drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein–protein interaction network identified 10 hub genes in the brown module <italic>LUC7L3</italic>, <italic>SNRNP70</italic>, <italic>PRPF3</italic>, <italic>LUC7L</italic>, <italic>CLASRP</italic>, <italic>CLK1</italic>, <italic>CLK2</italic>, <italic>U2AF1L4</italic>, <italic>NXF1</italic>, and <italic>THOC1</italic>) and 13 in the yellow module (<italic>PNN</italic>, <italic>PPWD1</italic>, <italic>SRRM2</italic>, <italic>DHX35</italic>, <italic>DMTF1</italic>, <italic>SALL4</italic>, <italic>MTA1</italic>, <italic>HDAC7</italic>, <italic>PHC1</italic>, <italic>ACIN1</italic>, <italic>HNRNPH1</italic>, <italic>DDX17</italic>, and <italic>HDAC6</italic>). The prognostic model composed of <italic>RNF207</italic>, <italic>REC8</italic>, <italic>DFNB59</italic>, <italic>HOXA2</italic>, <italic>EPOR</italic>, <italic>PILRB</italic>, <italic>LSMEM1</italic>, <italic>TCIRG1</italic>, <italic>ABTB1</italic>, <italic>ZNF276</italic>, <italic>ZNF540</italic>, and <italic>DPY19L2</italic> could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy.</p></sec><sec><title>Conclusion</title><p>In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.</p></sec>