Dataset Information

Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

ABSTRACT: Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract, which plays an important role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) have been shown to contribute to cancer risk and prognosis. However, the role of SNPs of MAGE-A11 in renal cell carcinoma (RCC) has not been established. Two intronic SNPs (rs6641352 and rs6540341) of MAGE-A11 have been screened to assess their associations with RCC risk and prognosis in a case control study. We found that rs6641352 was associated with RCC susceptibility in the dominant model (TC/CC vs. TT, adjusted odds ratio = 1.315, 95% confidence interval [CI] = 1.089-1.588) and with survival of RCC in the recessive model (CC vs. TT/TC, adjusted hazard ratio = 3.526, 95% CI = 1.072-11.595). For the SNP rs6540341, individuals with the T allele could have a critically increased risk of RCC (adjusted odds ratio = 1.301, 95% CI = 1.081-1.564, P = 0.005 in the dominant model). However, there was no significant association between rs6540341 and RCC survival. Hence, rs6641352 in MAGE-A11 may contribute to the genetic susceptibility and prognosis for RCC and act as a biomarker for RCC occurrence and prognosis.

SUBMITTER: Su S

PROVIDER: S-EPMC6775520 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

Su Shifeng S Gu Qi Q Xu Aiming A Shen Sipeng S Liu Shouyong S Zhang Chao C Miao Chengkui C Qin Chao C Liu Bianjiang B Wang Zengjun Z

Journal of Cancer 20190827 20

Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract, which plays an important role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) have been shown to contribute to cancer risk and prognosis. However, the role of SNPs of MAGE-A11 in renal cell carcinoma (RCC) has not been established. Two intronic SNPs (rs6641352 and rs6540341) of MAGE-A11 have been screened to assess thei ...[more]

PMID: 31598157

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Project description:Background:To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer (ccRCC) and investigate the immune-associated genes by a comprehensive analysis of The Cancer Genome Atlas (TCGA) database. Methods:We collected mRNA expression profiles of 537 ccRCC samples from the TCGA database. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. The differentially expressed genes (DEGs) were screened between high immune/stromal score and low immune/stromal score groups by the cutoff of |log (fold change)|?>?1, P value <0.05 by using package "limma" in R. Functional enrichment analysis was performed by DAVID, and the protein-protein interaction network of intersected DEGs between stromal score and immune score groups was conducted using the STRING database. The Kaplan-Meier method was used to explore DEGs with predictive values in overall survival, and the prognostic DEGs were further validated in a Gene Expression Omnibus (GEO) dataset GSE29609. Results:A higher immune score was associated with T3/4 (vs. T1/2, P < 0.001), N1 (vs. N0, P=0.05), M1 (vs. M0, P=0.004), G3/4 (vs. G1/2, P < 0.001), advanced AJCC stage (P < 0.001), and shorter overall survival (P=0.04). Intersected DEGs between immune and stromal score groups were 48 upregulated and 47 downregulated genes, with 43 DEGs associated with overall survival in ccRCC. After validation by a cohort of 39 ccRCC cases with detailed follow-up information from GSE29609, six immune-associated DEGs including CASP5, HSD11B1, VSIG4, HMGCS2, HSD11B2, and OGDHL were demonstrated to be predictive of prognosis in ccRCC. Conclusions:Our study elucidated tight associations between immune score and clinical characteristics as well as prognosis in ccRCC. Moreover, six DEGs were explored and validated to exert predictive values in overall survival of ccRCC.

Project description:ObjectiveLncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) is a newly identified lncRNA to promote the sunitinib resistance of renal cell carcinoma (RCC), which may contribute to tumorigenesis and progression. This study aimed to explore the association of lncARSR tagSNPs with the risk and prognosis of RCC.MethodsIn this study, a 2-stage case-control study was performed to evaluate the association between 2 tagging SNPs (rs1417080 and rs7859384) and RCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analyses. Different survival time was estimated by the Kaplan-Meier method and compared by the Log-rank test. Hazard ratios (HRs) and their 95% CIs were calculated to determine predictive factors by Cox proportion hazards model.ResultsWhen combing discovery and validation sets together, rs7859384 was determined to be significantly associated with the decreased RCC risk with all P < 0.05 in 4 models (co-dominant model, additive model, dominant model and recessive model). stratified analyses showed prominent risk effect of SNP rs7859384 GA/GG genotypes was found in clinical subgroups of stage I and stage II (P = 0.009, OR = 0.77, 95% CI = 0.64-0.94) and individuals with clear cell RCC (P = 0.014, OR = 0.79, 95% CI = 0.65-0.95). A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with BMI > 24 (P = 0.025, OR = 0.74, 95% CI = 0.56-0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63-0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68-1.00). Survival analyses revealed individuals with GA/GG genotypes had higher survival rate compared with the corresponding AA wild genotypes in the dominant model (log-rank P = 0.005, adjusted HR = 0.34, 95% CI = 0.16-0.73).ConclusionThis study suggests that rs7859384 of lncARSR was associated with RCC susceptibility and may act as a prognostic biomarker for patients with RCC.

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Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

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Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

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