Integrative Genomic Analysis for the Discovery of Biomarkers in Prostate Cancer

Hicks, Chindo; Koganti, Tejaswi; Giri, Shankar; Tekere, Memory; Ramani, Ritika; Sitthi-Amorn, Jitsuda; Vijayakumar, Srinivasan

doi:10.4137/bmi.s13729

Cited by 8 publications

(12 citation statements)

References 55 publications

(111 reference statements)

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“…Several studies have been conducted regarding the location of SNPs and the differences in their rates of occurrence by race. Approximately 100 genes with SNPs are implicated in increasing men’s susceptibility to prostate cancer [ 20 , 21 ]. These are especially accurate because SNPs are stable throughout one’s lifetime, so they cannot be affected by extraneous factors such as lifestyle [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Do African-American men need separate prostate cancer screening guidelines?

et al. 2016

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BackgroundIn 2012, the United States Preventative Services Task Force issued new guidelines recommending that male U.S. residents, irrespective of race, no longer be screened for prostate cancer. In African American men, the incidence of prostate cancer is almost 60 % higher and the mortality rate is two to three times greater than in Caucasians. The purpose of this study is to reduce African American men's prostate cancer burden by demonstrating they need separate screening guidelines.MethodsWe performed a PubMed search using the keywords: African American, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, PSA density, and to derive data relevant to our hypothesis.ResultsIn our literature review, we identified several aspects of prostate cancer that are different in Caucasian and African American men. These included prostate cancer incidence and outcome, the clinical course of the disease, serum PSA levels, genetic differences, and social barriers. It's also important to note that the USPSTF guidelines were based on two studies, one of which reported that only 4 % of its participants were African American. The other did not report demographic information, but used participants from seven European countries with small African American populations.ConclusionGiven the above, we conclude that separate prostate cancer screening guidelines are greatly necessary to help save the lives of African Americans.

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Section: Resultsmentioning

confidence: 99%

Do African-American men need separate prostate cancer screening guidelines?

et al. 2016

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“…To address this, we have developed a comprehensive catalogue of germline mutations and genes used in this report and continuously updated it [10, 22, 23, 26, 27]. The details regarding methods of data collection, curation, and annotation, including inclusion and exclusion criteria, have been described in our earlier publications [10, 22, 23, 26, 27] and were based on internationally accepted standards and guidelines proposed by the Human Genome Epidemiology Network for a systematic review of genetic associations [28–32]. The data in our catalogue were supplemented with information from the GWAS catalogue [9–13] which is continuously updated to ensure completeness of the germline variation data used in this study.…”

Section: Methodsmentioning

confidence: 99%

Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

Mamidi

Hicks

2019

Journal of Oncology

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Background A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

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“…7,22 Data collection was based on the guidelines proposed by the Human Genome Epidemiology Network for systematic review of genetic associations. 26–30 The details pertaining collection of data used in this study have been reported in our previous published reports.…”

Section: Methodsmentioning

confidence: 99%

“… 7 Indeed, several groups including ours have reported integration of GWAS information with gene expression data in prostate cancer. 20 – 25 However, the association of GWAS discoveries with primary organ–confined and metastatic disease has not been reported. Similarly, discovery of molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states has not been reported.…”

Section: Introductionmentioning

confidence: 99%

An Integrative Genomics Approach for Associating Genome-Wide Association Studies Information With Localized and Metastatic Prostate Cancer Phenotypes

et al. 2017

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High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate GWAS information of patients with primary organ–confined and metastatic prostate cancer using gene expression data and to identify molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states. The analysis revealed gene signatures for the 2 disease states and a gene signature distinguishing the 2 patient groups. In addition, the analysis revealed molecular networks and biological pathways enriched for genetic susceptibility variants. The discovered pathways include the androgen, apoptosis, and insulinlike growth factor signaling pathways. This analysis established putative functional bridges between GWAS discoveries and the biological pathways involved in primary organ–confined and metastatic prostate cancer.

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Integrative Genomic Analysis for the Discovery of Biomarkers in Prostate Cancer

Cited by 8 publications

References 55 publications

Do African-American men need separate prostate cancer screening guidelines?

Do African-American men need separate prostate cancer screening guidelines?

Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

An Integrative Genomics Approach for Associating Genome-Wide Association Studies Information With Localized and Metastatic Prostate Cancer Phenotypes

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