Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis
<b>Background:</b> Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20–40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially e...
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2024-12-01
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| author | Chi-Fen Chang Lih-Chyang Chen Yei-Tsung Chen Chao-Yuan Huang Chia-Cheng Yu Victor C. Lin Te-Ling Lu Shu-Pin Huang Bo-Ying Bao |
| author_facet | Chi-Fen Chang Lih-Chyang Chen Yei-Tsung Chen Chao-Yuan Huang Chia-Cheng Yu Victor C. Lin Te-Ling Lu Shu-Pin Huang Bo-Ying Bao |
| author_sort | Chi-Fen Chang |
| collection | DOAJ |
| description | <b>Background:</b> Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20–40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially expressed in normal and neoplastic cell (<i>DENN</i>) domain-containing genes in oncogenesis; however, their implications in prostate cancer and BCR risk remain underexplored. <b>Methods:</b> This study systematically evaluated 151 single-nucleotide polymorphisms in <i>DENN</i> domain-containing genes in 458 patients with prostate cancer and BCR, followed by validation in an independent cohort of 185 patients. <b>Results:</b> Multivariate Cox regression analyses identified <i>DENND2D</i> rs610261 G>A as significantly associated with improved BCR-free survival in both cohorts (adjusted hazard ratio = 0.39, 95% confidence interval = 0.23–0.66, <i>p</i> = 0.001). Functional analysis revealed rs610261’s regulatory potential, with the protective A allele correlating with increased <i>DENND2D</i> expression in various human tissues. Compared to normal prostate tissues, <i>DENND2D</i> expression was reduced in prostate cancer, with higher expression being linked to favorable patient prognosis (<i>p</i> = 0.03). Gene set enrichment analysis revealed an association between <i>DENND2D</i> expression and the negative regulation of <i>MYC</i> target genes, including <i>MAD2L1</i>, <i>ERH</i>, and <i>CLNS1A</i>, which are overexpressed in prostate cancer and associated with poor survival. Furthermore, the elevated <i>DENND2D</i> expression promotes immune infiltration in prostate cancer, supporting its role in immune modulation. <b>Conclusions:</b> <i>DENND2D</i> is a prognostic biomarker for BCR in prostate cancer and offers new avenues for personalized treatment strategies. |
| format | Article |
| id | doaj-art-f401c33d20c1406c8e3c812be1e351a4 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-f401c33d20c1406c8e3c812be1e351a42025-01-24T13:23:45ZengMDPI AGBiomedicines2227-90592024-12-011312510.3390/biomedicines13010025Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to PrognosisChi-Fen Chang0Lih-Chyang Chen1Yei-Tsung Chen2Chao-Yuan Huang3Chia-Cheng Yu4Victor C. Lin5Te-Ling Lu6Shu-Pin Huang7Bo-Ying Bao8Department of Anatomy, School of Medicine, China Medical University, Taichung 406, TaiwanDepartment of Medicine, Mackay Medical College, New Taipei City 252, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanDepartment of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, TaiwanDivision of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, TaiwanDepartment of Urology, E-Da Hospital, Kaohsiung 824, TaiwanDepartment of Pharmacy, China Medical University, Taichung 404, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Pharmacy, China Medical University, Taichung 404, Taiwan<b>Background:</b> Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20–40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially expressed in normal and neoplastic cell (<i>DENN</i>) domain-containing genes in oncogenesis; however, their implications in prostate cancer and BCR risk remain underexplored. <b>Methods:</b> This study systematically evaluated 151 single-nucleotide polymorphisms in <i>DENN</i> domain-containing genes in 458 patients with prostate cancer and BCR, followed by validation in an independent cohort of 185 patients. <b>Results:</b> Multivariate Cox regression analyses identified <i>DENND2D</i> rs610261 G>A as significantly associated with improved BCR-free survival in both cohorts (adjusted hazard ratio = 0.39, 95% confidence interval = 0.23–0.66, <i>p</i> = 0.001). Functional analysis revealed rs610261’s regulatory potential, with the protective A allele correlating with increased <i>DENND2D</i> expression in various human tissues. Compared to normal prostate tissues, <i>DENND2D</i> expression was reduced in prostate cancer, with higher expression being linked to favorable patient prognosis (<i>p</i> = 0.03). Gene set enrichment analysis revealed an association between <i>DENND2D</i> expression and the negative regulation of <i>MYC</i> target genes, including <i>MAD2L1</i>, <i>ERH</i>, and <i>CLNS1A</i>, which are overexpressed in prostate cancer and associated with poor survival. Furthermore, the elevated <i>DENND2D</i> expression promotes immune infiltration in prostate cancer, supporting its role in immune modulation. <b>Conclusions:</b> <i>DENND2D</i> is a prognostic biomarker for BCR in prostate cancer and offers new avenues for personalized treatment strategies.https://www.mdpi.com/2227-9059/13/1/25prostate cancerrecurrence<i>DENN</i> domain-containing genesgene set enrichment analysisbiomarker |
| spellingShingle | Chi-Fen Chang Lih-Chyang Chen Yei-Tsung Chen Chao-Yuan Huang Chia-Cheng Yu Victor C. Lin Te-Ling Lu Shu-Pin Huang Bo-Ying Bao Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis Biomedicines prostate cancer recurrence <i>DENN</i> domain-containing genes gene set enrichment analysis biomarker |
| title | Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis |
| title_full | Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis |
| title_fullStr | Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis |
| title_full_unstemmed | Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis |
| title_short | Unveiling <i>DENND2D</i> as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis |
| title_sort | unveiling i dennd2d i as a novel prognostic biomarker for prostate cancer recurrence from gene to prognosis |
| topic | prostate cancer recurrence <i>DENN</i> domain-containing genes gene set enrichment analysis biomarker |
| url | https://www.mdpi.com/2227-9059/13/1/25 |
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