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Integrated analysis identifies GABRB3 as a biomarker in prostate cancer.
Chen, Jun-Yan; Chang, Chi-Fen; Huang, Shu-Pin; Huang, Chao-Yuan; Yu, Chia-Cheng; Lin, Victor C; Geng, Jiun-Hung; Li, Chia-Yang; Lu, Te-Ling; Bao, Bo-Ying.
Afiliación
  • Chen JY; Department of Pharmacy, China Medical University, 100 Jingmao Road Section 1, 406, Taichung, Taiwan.
  • Chang CF; Department of Anatomy, School of Medicine, China Medical University, 406, Taichung, Taiwan.
  • Huang SP; Department of Urology, Kaohsiung Medical University Hospital, 807, Kaohsiung, Taiwan.
  • Huang CY; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 807, Kaohsiung, Taiwan.
  • Yu CC; Institute of Medical Science and Technology, College of Medicine , National Sun Yat-Sen University, 804, Kaohsiung, Taiwan.
  • Lin VC; Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, 100, Taipei, Taiwan.
  • Geng JH; Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan.
  • Li CY; Department of Urology, School of Medicine, National Yang Ming Chiao Tung University , 112, Taipei, Taiwan.
  • Lu TL; Department of Pharmacy, Tajen University, 907, Pingtung, Taiwan.
  • Bao BY; Department of Urology, E-Da Hospital, 824, Kaohsiung, Taiwan.
BMC Med Genomics ; 17(1): 41, 2024 Jan 29.
Article en En | MEDLINE | ID: mdl-38287309
ABSTRACT

BACKGROUND:

Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer.

METHODS:

We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer.

RESULTS:

After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer.

CONCLUSION:

Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: BMC Med Genomics Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: BMC Med Genomics Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM