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ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.

ABSTRACT: An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC.We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between patients with (n = 23) and without (n = 42) a history of smoking. Analyses were first stratified on obesity status (the other primary risk factor for ccRCC) and then combined and analyzed together. To identify genes where the fold change in smokers relative to non-smokers was different in tumor tissues in comparison to patient-matched normal kidney tissues, we identified Affymetrix probesets that had a significant tissue type-by-smoking status interaction pvalue. We then performed RT-PCR validation on the top eight candidate genes in an independent sample of 28 smokers and 54 non-smokers.We identified 15 probesets that mapped to eight genes that had candidate associations with smoking-related ccRCC: ANKS1B, ACOT6, PPWD1, EYS, LIMCH1, CHRNA6, MT1G, and ZNF600. Using RT-PCR, we validated that expression of ANKS1B is preferentially down-regulated in smoking-related ccRCC.We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. Thus, ANKS1B should be explored further as a novel avenue for early detection as well as prevention of ccRCC in smokers.

SUBMITTER: Eckel-Passow JE

PROVIDER: S-EPMC3944917 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.

Eckel-Passow Jeanette E JE Serie Daniel J DJ Bot Brian M BM Joseph Richard W RW Cheville John C JC Parker Alexander S AS

BMC urology 20140131

<h4>Background</h4>An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC.<h4>Methods</h4>We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between p ...[more]

PMID: 24479813

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Project description:Background: Histone acetylation modification has been found to be correlated the development of renal carcinoma; however, its role in clear cell renal carcinoma (ccRCC) remains to be investigated. Thus, this study aimed to identify the molecular subtypes and establish a relevant score based on histone acetylation modification in ccRCC. Methods: Gene expression and mutation data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on histone acetylation regulators expression, and the molecular and clinical characteristics including survival, tumor microenvironment, gene set variation, immune cell infiltration, and immune checkpoints in each subtype were investigated. Next, we employed univariate Cox analysis to analyze these genes and established acetylation-related score by lasso regression analysis. Furthermore, we investigated the differences including survival, signaling pathways, mutational landscape, and tumor mutation burden (TMB) between high-risk and low-risk groups. The established score was validated by receiver operating curve and univariate and multivariate Cox regression analyses. We also established a nomogram including acetylation score, age, gender, grade, and stage and verified it by decision curve analysis and calibration plot. The E-MTAB-1980 cohort from the ArrayExpress database was employed as a reference to validate the established score. Results: Thirty-three types of histone acetylation regulators were employed in this study, and two clusters were identified. The two clusters presented significant differences in survival, tumor microenvironment, immune cell infiltration, immune checkpoints, and signaling pathways. Furthermore, an acetylation-related score, composed of six genes (BRD9, HDAC10, KAT2A, KAT5, BRDT, SIRT1, KAT6A, HDAC5), was verified to be significantly associated with prognosis and TMB. Thus, the established scores were successfully verified by the validated cohort, and the nomogram was constructed and successfully validated. Conclusion: The identification of the histone acetylation-related subtypes and score in our study may help reveal the potential relation between histone acetylation and immunity and provide novel insights for the development of individualized therapy for ccRCC.

Dataset Information

ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.

Publications

ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.

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