Yuan-Chin Tsai1, Chao-Yuan Huang2, Yu-Mei Hsueh3, Yu-Ching Fan4, Yu-Cin Fong5, Shu-Pin Huang6, Jiun-Hung Geng7, Lih-Chyang Chen8, Te-Ling Lu9, Bo-Ying Bao10. 1. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan. 2. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan. 3. Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. 4. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan. 5. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. 6. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan. 7. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan. 8. Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan. 9. Department of Pharmacy, China Medical University, Taichung 406, Taiwan. 10. Department of Pharmacy, China Medical University, Taichung 406, Taiwan; Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan; Department of Nursing, Asia University, Taichung 413, Taiwan. Electronic address: bao@mail.cmu.edu.tw.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: After multiple testing correction and multivariate analysis, the minor T allele of MAPK10rs12648265 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. SIGNIFICANCE: In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.
Authors: Chi-Fen Chang; Shu-Pin Huang; Yu-Mei Hsueh; Jiun-Hung Geng; Chao-Yuan Huang; Bo-Ying Bao Journal: Int J Environ Res Public Health Date: 2022-09-30 Impact factor: 4.614