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MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer.

ABSTRACT: Incidence and mortality rates for prostate cancer are higher in African-American (AA) men than in European-American (EA) men, but the biologic basis for this disparity is unclear. We carried out a detailed analysis of gene expression changes in prostate cancer compared with their matched benign tissues in a cohort of AA men and compared them with existing data from EA men. In this manner, we identified MNX1 as a novel oncogene upregulated to a relatively greater degree in prostate cancer from AA men. Androgen and AKT signaling play a central role in the pathogenesis of prostate cancer and we found that both of these signaling pathways increased MNX1 expression. MNX1 in turn upregulated lipid synthesis by stimulating expression of SREBP1 and fatty acid synthetase. Our results define MNX1 as a novel targetable oncogene increased in AA prostate cancer that is associated with aggressive disease. Cancer Res; 76(21); 6290-8. ©2016 AACR.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5093064 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer.

Zhang Li L Wang Jianghua J Wang Yongquan Y Zhang Yiqun Y Castro Patricia P Shao Longjiang L Sreekumar Arun A Putluri Nagireddy N Guha Nilanjan N Deepak Saligrama S Padmanaban Arunkumar A Creighton Chad J CJ Ittmann Michael M

Cancer research 20160830 21

Incidence and mortality rates for prostate cancer are higher in African-American (AA) men than in European-American (EA) men, but the biologic basis for this disparity is unclear. We carried out a detailed analysis of gene expression changes in prostate cancer compared with their matched benign tissues in a cohort of AA men and compared them with existing data from EA men. In this manner, we identified MNX1 as a novel oncogene upregulated to a relatively greater degree in prostate cancer from AA ...[more]

PMID: 27578002

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Dataset Information

MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer.

Publications

MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer.

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