Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.
Background: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods: We performed molecular profiling...
| Publicado en: | Nutrition & Metabolism Vol. 21; no. 1; pp. 1 - 18 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
BioMed Central
4/2/2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=176405915&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 176405915 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17437075 1CYX jtl: Nutrition & Metabolism issn: 17437075 maglogo: N pubinfo: dt: 4/2/2024 vid: 21 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 176405915 176405915 176405915 10.1186/s12986-024-00791-2 176405915 ppf: 1 ppct: 17 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer. aug: au: Ding, Lei Wang, Yong Tang, Zhentao Ni, Chenbo Zhang, Qian Zhai, Qidi Liang, Chao Li, Jie affil: https://ror.org/04py1g812 Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210009, Nanjing, China sug: subj: Prostatic Neoplasms Prognosis Prostatic Neoplasms Drug Therapy Hormone Therapy Methods Vitamin D Blood Metabolites Vitamin D Metabolism Signal Transduction Prostatic Neoplasms Metabolism Tumor Markers, Biological Metabolism Genomics Human Male Female Funding Source Cancer Patients Cell Physiology Receptors, Cell Surface Gene Expression Profiling Regression Immune System Mutation Apolipoproteins Blood Biochemical Phenomena Proteins Male Female ab: Background: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. Results: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. Conclusion: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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