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Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer
BACKGROUND: The 5-year survival rate of patients with lung cancer in China is less than 20% and predicting their prognosis is challenging. We investigated the association between a common non-synonymous single nucleotide polymorphism (SNP), rs7214723, in the Ca(2+)/calmodulin-dependent protein kinas...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640188/ https://www.ncbi.nlm.nih.gov/pubmed/34868969 http://dx.doi.org/10.3389/fonc.2021.757484 |
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author | Zhang, Haorui Chen, Bocen Zou, Zixiu Feng, Jian Li, Yutao Wang, Yi He, Xing Xu, Chang Wang, Haijian Guo, Shicheng Jin, Li Li, Qiang Wang, Jiucun Xiao, Man Li, Feng Wu, Junjie |
author_facet | Zhang, Haorui Chen, Bocen Zou, Zixiu Feng, Jian Li, Yutao Wang, Yi He, Xing Xu, Chang Wang, Haijian Guo, Shicheng Jin, Li Li, Qiang Wang, Jiucun Xiao, Man Li, Feng Wu, Junjie |
author_sort | Zhang, Haorui |
collection | PubMed |
description | BACKGROUND: The 5-year survival rate of patients with lung cancer in China is less than 20% and predicting their prognosis is challenging. We investigated the association between a common non-synonymous single nucleotide polymorphism (SNP), rs7214723, in the Ca(2+)/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer. METHODS: Genomic DNA was extracted from the blood samples of 839 patients with lung cancer, recruited from Changhai Hospital (n = 536) and Taizhou Institute of Health Sciences (n = 352), and genotyped using the SNPscan technique. The association between patient prognosis and the genotypic data for CAMKK1 was analyzed using a multivariate Cox proportional hazards model adjusted for multiple potential confounders. The CRISPR/Cas9 gene-editing system was used to introduce point mutations in the CAMKK1 rs7214723 of A549 and NCI-H358 cells. Subsequently, Cell proliferation and migration ability were assessed with the Cell Counting Kit-8 and scratch assay. The Annexin V-FITC apoptosis detection kit was used to detect cell apoptosis. RESULTS: The CAMKK1 rs7214723 recessive CC genotype conferred significantly better overall survival (CC vs. TT + TC: adjusted hazard ratio = 0.78, 95% confidence interval [CI], 0.61-1.00, P = 0.049) than the TT + TC genotypes. Stratified analysis showed that the CAMKK1 rs7214723 CC genotype and recessive CC genotype conferred a significantly decreased risk of death in patients who were male, had a smoking history, or had stage III + IV cancer, compared with the TT and TT + TC genotypes. Relative to the TT + TC genotypes, the rs7214723 recessive CC genotype was also associated with a decreased risk of death in patients aged < 60 years (CC vs. TT + TC: adjusted hazard ratio = 0.59, 95% CI, 0.37-0.93, P = 0.024) and patients with squamous cell carcinoma (CC vs. TT + TC: adjusted hazard ratio = 0.65, 95% CI, 0.44-0.98, P = 0.038). Remarkably, CRISPR/Cas9-guided single nucleotide editing demonstrated that CAMKK1 rs7214723 T > C mutation significantly inhibits cell proliferation and migration and promotes cell apoptosis. CONCLUSIONS: CAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer. |
format | Online Article Text |
id | pubmed-8640188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86401882021-12-04 Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer Zhang, Haorui Chen, Bocen Zou, Zixiu Feng, Jian Li, Yutao Wang, Yi He, Xing Xu, Chang Wang, Haijian Guo, Shicheng Jin, Li Li, Qiang Wang, Jiucun Xiao, Man Li, Feng Wu, Junjie Front Oncol Oncology BACKGROUND: The 5-year survival rate of patients with lung cancer in China is less than 20% and predicting their prognosis is challenging. We investigated the association between a common non-synonymous single nucleotide polymorphism (SNP), rs7214723, in the Ca(2+)/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer. METHODS: Genomic DNA was extracted from the blood samples of 839 patients with lung cancer, recruited from Changhai Hospital (n = 536) and Taizhou Institute of Health Sciences (n = 352), and genotyped using the SNPscan technique. The association between patient prognosis and the genotypic data for CAMKK1 was analyzed using a multivariate Cox proportional hazards model adjusted for multiple potential confounders. The CRISPR/Cas9 gene-editing system was used to introduce point mutations in the CAMKK1 rs7214723 of A549 and NCI-H358 cells. Subsequently, Cell proliferation and migration ability were assessed with the Cell Counting Kit-8 and scratch assay. The Annexin V-FITC apoptosis detection kit was used to detect cell apoptosis. RESULTS: The CAMKK1 rs7214723 recessive CC genotype conferred significantly better overall survival (CC vs. TT + TC: adjusted hazard ratio = 0.78, 95% confidence interval [CI], 0.61-1.00, P = 0.049) than the TT + TC genotypes. Stratified analysis showed that the CAMKK1 rs7214723 CC genotype and recessive CC genotype conferred a significantly decreased risk of death in patients who were male, had a smoking history, or had stage III + IV cancer, compared with the TT and TT + TC genotypes. Relative to the TT + TC genotypes, the rs7214723 recessive CC genotype was also associated with a decreased risk of death in patients aged < 60 years (CC vs. TT + TC: adjusted hazard ratio = 0.59, 95% CI, 0.37-0.93, P = 0.024) and patients with squamous cell carcinoma (CC vs. TT + TC: adjusted hazard ratio = 0.65, 95% CI, 0.44-0.98, P = 0.038). Remarkably, CRISPR/Cas9-guided single nucleotide editing demonstrated that CAMKK1 rs7214723 T > C mutation significantly inhibits cell proliferation and migration and promotes cell apoptosis. CONCLUSIONS: CAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8640188/ /pubmed/34868969 http://dx.doi.org/10.3389/fonc.2021.757484 Text en Copyright © 2021 Zhang, Chen, Zou, Feng, Li, Wang, He, Xu, Wang, Guo, Jin, Li, Wang, Xiao, Li and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhang, Haorui Chen, Bocen Zou, Zixiu Feng, Jian Li, Yutao Wang, Yi He, Xing Xu, Chang Wang, Haijian Guo, Shicheng Jin, Li Li, Qiang Wang, Jiucun Xiao, Man Li, Feng Wu, Junjie Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title | Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title_full | Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title_fullStr | Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title_full_unstemmed | Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title_short | Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
title_sort | associations between camkk1 polymorphism rs7214723 and the prognosis of patients with lung cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640188/ https://www.ncbi.nlm.nih.gov/pubmed/34868969 http://dx.doi.org/10.3389/fonc.2021.757484 |
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