OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer

Purpose: This study aimed to identify metabolic genes associated with non-metastatic prostate cancer progression using The Cancer Genome Atlas (TCGA) datasets and validate their prognostic role by assessing patients’ immunohistochemical prostatectomy specimens. Materials and Methods: Several meta...

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Main Authors: Sung Han Kim, Jae Young Joung, Weon Seo Park, Jongkeun Park, Jin Seok Lee, Boram Park, Dongwan Hong
Format: Article
Language:English
Published: Korean Society for Sexual Medicine and Andrology 2023-07-01
Series:The World Journal of Men's Health
Subjects:
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author Sung Han Kim
Jae Young Joung
Weon Seo Park
Jongkeun Park
Jin Seok Lee
Boram Park
Dongwan Hong
author_facet Sung Han Kim
Jae Young Joung
Weon Seo Park
Jongkeun Park
Jin Seok Lee
Boram Park
Dongwan Hong
author_sort Sung Han Kim
collection DOAJ
description Purpose: This study aimed to identify metabolic genes associated with non-metastatic prostate cancer progression using The Cancer Genome Atlas (TCGA) datasets and validate their prognostic role by assessing patients’ immunohistochemical prostatectomy specimens. Materials and Methods: Several metabolic candidate genes analyzed were highly correlated with cancer progression to biochemical recurrence (BCR) and deaths in 335 patients’ genetic information from TCGA datasets. Those candidate genes and their expressions in tissue specimens were validated retrospectively by immunohistochemical analysis of radical prostatectomy specimens collected from 514 consecutive patients with non-metastatic prostate cancer between 2000 and 2015. The Cox proportional-hazards model was used to predict the prognostic role of each candidate gene expression in BCR and survival prognoses with a statistical significance of p-value <0.05. Twenty metabolic genes were identified by own developed software (Targa; https://github.com/cgab-ncc/TarGA), whose median expression levels consistently increased with cancer progression to the BCR and deaths. Results: Five metabolic genes (MAT2A, FLAD1, UGDH, OGT, and RRM2) were found to be significantly involved in the overall survival in the TCGA dataset. The immunohistochemical validation and clinicopathological data showed that OGT (hazard ratio [HR], 1.002; 95% confidence interval [CI], 1.001–1.003) and FLAD1 (HR, 1.010; 95% CI, 1.003–1.017) remained significant factors for BCR and cancer-specific survival, respectively, in the multivariate analysis even after adjusting for confounding clinicopathological parameters (p<0.05). Conclusions: OGT and FLAD1 showed significant prognostic factors of disease progression, even after adjustment for confounding clinicopathological parameters in non-metastatic prostate cancer.
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spelling doaj.art-c85c5668f00046f894b7462e8a9065872023-06-20T02:47:57ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902023-07-0141371272310.5534/wjmh.220231OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate CancerSung Han Kim0https://orcid.org/0000-0002-1689-5203Jae Young Joung1https://orcid.org/0000-0002-7971-211XWeon Seo Park2https://orcid.org/0000-0002-0035-1455Jongkeun Park3https://orcid.org/0000-0001-8311-6655Jin Seok Lee4https://orcid.org/0000-0003-4120-8708Boram Park5https://orcid.org/0000-0003-2683-8795Dongwan Hong6https://orcid.org/0000-0002-7816-1299Department of Urology, Center for Urological Cancer, National Cancer Center, GoyangDepartment of Urology, Center for Urological Cancer, National Cancer Center, GoyangNational Cancer Center, GoyangDepartment of Medical Informatics, College of Medicine, The Catholic University, SeoulDepartment of Medical Informatics, College of Medicine, The Catholic University, SeoulResearch Institute, National Cancer Center, Goyanghttps://orcid.org/0000-0003-4120-8708Purpose: This study aimed to identify metabolic genes associated with non-metastatic prostate cancer progression using The Cancer Genome Atlas (TCGA) datasets and validate their prognostic role by assessing patients’ immunohistochemical prostatectomy specimens. Materials and Methods: Several metabolic candidate genes analyzed were highly correlated with cancer progression to biochemical recurrence (BCR) and deaths in 335 patients’ genetic information from TCGA datasets. Those candidate genes and their expressions in tissue specimens were validated retrospectively by immunohistochemical analysis of radical prostatectomy specimens collected from 514 consecutive patients with non-metastatic prostate cancer between 2000 and 2015. The Cox proportional-hazards model was used to predict the prognostic role of each candidate gene expression in BCR and survival prognoses with a statistical significance of p-value <0.05. Twenty metabolic genes were identified by own developed software (Targa; https://github.com/cgab-ncc/TarGA), whose median expression levels consistently increased with cancer progression to the BCR and deaths. Results: Five metabolic genes (MAT2A, FLAD1, UGDH, OGT, and RRM2) were found to be significantly involved in the overall survival in the TCGA dataset. The immunohistochemical validation and clinicopathological data showed that OGT (hazard ratio [HR], 1.002; 95% confidence interval [CI], 1.001–1.003) and FLAD1 (HR, 1.010; 95% CI, 1.003–1.017) remained significant factors for BCR and cancer-specific survival, respectively, in the multivariate analysis even after adjusting for confounding clinicopathological parameters (p<0.05). Conclusions: OGT and FLAD1 showed significant prognostic factors of disease progression, even after adjustment for confounding clinicopathological parameters in non-metastatic prostate cancer.big datametabolismprostate cancertumor staging
spellingShingle Sung Han Kim
Jae Young Joung
Weon Seo Park
Jongkeun Park
Jin Seok Lee
Boram Park
Dongwan Hong
OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
The World Journal of Men's Health
big data
metabolism
prostate cancer
tumor staging
title OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
title_full OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
title_fullStr OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
title_full_unstemmed OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
title_short OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer
title_sort ogt and flad1 genes had significant prognostic roles in progressive pathogenesis in prostate cancer
topic big data
metabolism
prostate cancer
tumor staging
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