Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes

The mitogen-activated protein kinase (MAPK) cascades integrate various upstream signals to regulate many cellular functions, including proliferation, differentiation, and survival. Dysregulation of these pathways has been implicated in the occurrence and progression of a variety of cancers. This stu...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2021-06, Vol.275, p.119396-119396, Article 119396
Main Authors: Tsai, Yuan-Chin, Huang, Chao-Yuan, Hsueh, Yu-Mei, Fan, Yu-Ching, Fong, Yu-Cin, Huang, Shu-Pin, Geng, Jiun-Hung, Chen, Lih-Chyang, Lu, Te-Ling, Bao, Bo-Ying
Format: Article
Language:English
Subjects:
Aged
Alleles
Anisomycin
Biomarkers
Blotting, Western
Cancer
Carcinoma, Renal Cell - genetics
Case-Control Studies
Cell Line, Tumor
Clinical outcomes
Confidence intervals
Female
Genetic diversity
Genetic Predisposition to Disease - genetics
Genetic susceptibility
Genetic variance
Humans
Kidney cancer
Kidney Neoplasms - genetics
Kinases
Male
MAP kinase
Medical prognosis
Metastases
Middle Aged
Mitogen-activated protein kinase
Mitogen-Activated Protein Kinase 10 - genetics
Multivariate analysis
Nucleotides
Polymorphism, Single Nucleotide - genetics
Protein kinase
Renal cell carcinoma
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Survival
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The mitogen-activated protein kinase (MAPK) cascades integrate various upstream signals to regulate many cellular functions, including proliferation, differentiation, and survival. Dysregulation of these pathways has been implicated in the occurrence and progression of a variety of cancers. This study aimed to assess the association of 192 single nucleotide polymorphisms in 22 MAPK cascade genes with renal cell carcinoma (RCC) risk and survival in 312 patients and 318 controls. After multiple testing correction and multivariate analysis, the minor T allele of MAPK10 rs12648265 remained associated with a lower risk of RCC (adjusted odds ratio 0.64, 95% confidence interval 0.50–0.82, P = 0.000426) and metastasis (adjusted hazard ratio 0.50, 95% confidence interval 0.30–0.82, P = 0.006). Presence of the rs12648265 T allele demonstrated a trend towards being associated with increased MAPK10 expression, and meta-analysis of four RCC datasets indicated that high MAPK10 expression is associated with a favourable prognosis. Furthermore, activation of MAPK10 by the potent agonist anisomycin inhibited RCC cell growth in vitro, suggesting an involvement of MAPK10 in RCC progression. In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.119396