PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity

Canto, Patricia; Granados, Jesús Benítez; Feria-Bernal, Guillermo; Coral‐Vázquez, Ramón Mauricio; García-García, Eduardo; Tejeda, María Elena; Tapia, André; Rojano-Mejía, David; Méndez, Juan Pablo

doi:10.3233/cbm-160467

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…RORC encoding ROR-γ could induce androgen expression in prostate cancer [37] and is a potential therapeutic target in castration-resistant prostate cancer [38]. PPARGC1A and ZFHX3 are also reported to be associated with prostate cancer [39,40], which could partly explain their ability to predict relapse risk. This research has several practical meanings for clinical management of PRAD patients.…”

Section: Discussionmentioning

confidence: 99%

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

Liu

Zhao

Yang

et al. 2022

Aging

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Prostate adenocarcinoma (PRAD) represents the most common male carcinoma in developed countries, its high relapse risk contributes to the second-leading cause of cancer-related deaths. Therefore, it is required to develop an effective signature for predicting the relapse risk of PRAD. To identify a circadian rhythm-(CR-) related predictive signature, we analyzed RNA-seq data of patients with prostate adenocarcinoma (PRAD) from the TCGA and GEO cohort. Seven circadian rhythm-(CR-) related genes (FBXL22, MTA1, TP53, RORC, DRD4, PPARGC1A, ZFHX3) were eventually identified to develop a CR-related signature. AUCs for 3-year overall survival were 0.852, 0.856 and 0.944 in the training set, validation set and an external independent test set (GSE70768), respectively. Kaplan-Meier curve analysis showed that the high-risk group has a reduced relapse-free survival (RFS) than the low-risk group in the training set, validation set, and test set, respectively (P < 0.05). We constructed a prognostic nomogram combining the CR-related signature with T staging to precisely estimate relapse risk of PRAD patients. Finally, we observed that the CR-related gene signature was associated with tumor mutation burden, multiple immune checkpoint molecules and microsatellite instability, and thus could predict response to immune checkpoint inhibitors in PRAD. Conclusively, we developed a circadian rhythm-related gene signature for predicting RFS and immunotherapy efficacy in prostate adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

Liu

Zhao

Yang

et al. 2022

Aging

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“…Filtering those group/cohort relationships identified the most altered genes in the local tumor cohorts (MSKCC and TCGA). Overlapping identified commonly altered genes associated with PCa including ERG 35 (which was also altered at the protein level in the OICR cohort) and FGFR2 95 , but also identified others that were relatively under-investigated such as PPARGC1A 37 , 38 , 96 but associated with worse disease free survival, or uninvestigated in PCa, such as the metastasis suppressor PDLIM1 97 . Stable knockdown of PGC1α increased proliferation and invasion of LNCaP cells, and profoundly altered the transcriptome.…”

Section: Discussionmentioning

confidence: 99%

Identification of transcription factor co-regulators that drive prostate cancer progression

Siddappa

Wani

Long

et al. 2020

Sci Rep

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In prostate cancer (PCa), and many other hormone-dependent cancers, there is clear evidence for distorted transcriptional control as disease driver mechanisms. Defining which transcription factor (TF) and coregulators are altered and combine to become oncogenic drivers remains a challenge, in part because of the multitude of TFs and coregulators and the diverse genomic space on which they function. The current study was undertaken to identify which TFs and coregulators are commonly altered in PCa. We generated unique lists of TFs (n = 2662), coactivators (COA; n = 766); corepressors (COR; n = 599); mixed function coregulators (MIXED; n = 511), and to address the challenge of defining how these genes are altered we tested how expression, copy number alterations and mutation status varied across seven prostate cancer (PCa) cohorts (three of localized and four advanced disease). Testing of significant changes was undertaken by bootstrapping approaches and the most significant changes were identified. For one commonly and significantly altered gene were stably knocked-down expression and undertook cell biology experiments and RNA-Seq to identify differentially altered gene networks and their association with PCa progression risks. COAS, CORS, MIXED and TFs all displayed significant down-regulated expression (q.value < 0.1) and correlated with protein expression (r 0.4–0.55). In localized PCa, stringent expression filtering identified commonly altered TFs and coregulator genes, including well-established (e.g. ERG) and underexplored (e.g. PPARGC1A, encodes PGC1α). Reduced PPARGC1A expression significantly associated with worse disease-free survival in two cohorts of localized PCa. Stable PGC1α knockdown in LNCaP cells increased growth rates and invasiveness and RNA-Seq revealed a profound basal impact on gene expression (~ 2300 genes; FDR < 0.05, logFC > 1.5), but only modestly impacted PPARγ responses. GSEA analyses of the PGC1α transcriptome revealed that it significantly altered the AR-dependent transcriptome, and was enriched for epigenetic modifiers. PGC1α-dependent genes were overlapped with PGC1α-ChIP-Seq genes and significantly associated in TCGA with higher grade tumors and worse disease-free survival. These methods and data demonstrate an approach to identify cancer-driver coregulators in cancer, and that PGC1α expression is clinically significant yet underexplored coregulator in aggressive early stage PCa.

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“…ADIPOQ encodes an adipocytokine, adiponectin, which is essential for metabolic and hormonal processes (27). A low level of plasma adiponectin has been significantly associated with several types of cancer, including colorectal and prostate cancer (28,29). It was also reported that adiponectin may decrease cancer cell growth by promoting the activity of autophagosomes and decreasing the sequestosome 1/GAP-associated tyrosine phosphoprotein p62 signaling pathway in BC (27).…”

Section: Discussionmentioning

confidence: 99%

Analysis of key genes and pathways in breast ductal carcinoma <em>in situ</em>

Zhao

2020

Oncol Lett

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Breast cancer (BC) remains the most common cancer in females. Therefore, the present study aimed to identify key genes involved in the carcinogenesis of BC and to explore their prognostic values by integrating bioinformatics tools. The gene expression profiles of 46 ductal carcinoma in situ (DCIS) and three normal breast tissues from the GSE59248 dataset were downloaded. Differentially expressed genes (DEGs) were subsequently identified using the online tool GEO2R and a functional enrichment analysis was performed. In addition, a protein-protein interaction (PPI) network was constructed and the top eight hub genes were identified. The prognostic values of the hub genes were further investigated. A total of 316 DEGs, including 32 upregulated and 284 downregulated genes, were identified. Furthermore, eight hub genes, including lipase E hormone sensitive type, patatin like phospholipase domain containing 2, adiponectin C1Q and collagen domain containing (ADIPOQ), peroxisome proliferator activated receptor γ (PPARG), fatty acid binding protein 4 (FABP4), diacylglycerol O-acyltransferase 2, lipoprotein lipase (LPL) and leptin (LEP), were identified from the PPI network. The downregulated expression of ADIPOQ, PPARG, FABP4, LPL and LEP was significantly associated with poor overall survival in patients with DCIS. Therefore, these genes may serve as potential biomarkers for prognosis prediction. However, further investigation is required to validate the results obtained in the present study.

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PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity

Abstract: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Cited by 7 publications

References 34 publications

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

Identification of transcription factor co-regulators that drive prostate cancer progression

Analysis of key genes and pathways in breast ductal carcinoma <em>in situ</em>

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PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity

Abstract: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Cited by 7 publications

References 34 publications

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

Identification of transcription factor co-regulators that drive prostate cancer progression

Analysis of key genes and pathways in breast ductal carcinoma <em>in&nbsp;situ</em>

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Analysis of key genes and pathways in breast ductal carcinoma <em>in situ</em>