Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer
BackgroundThe 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 Ca2+/calmodulin-dependent protein kinase ki...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:9ae897a769dd4b8995dc1c624a2f05c72021-11-19T06:19:22ZAssociations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer2234-943X10.3389/fonc.2021.757484https://doaj.org/article/9ae897a769dd4b8995dc1c624a2f05c72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.757484/fullhttps://doaj.org/toc/2234-943XBackgroundThe 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 Ca2+/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer.MethodsGenomic 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.ResultsThe 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.ConclusionsCAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer.Haorui ZhangBocen ChenZixiu ZouJian FengYutao LiYi WangXing HeChang XuHaijian WangShicheng GuoLi JinLi JinQiang LiJiucun WangJiucun WangMan XiaoFeng LiJunjie WuJunjie WuJunjie WuFrontiers Media S.A.articleCAMKK1rs7214723single nucleotide polymorphismlung cancerprognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
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CAMKK1 rs7214723 single nucleotide polymorphism lung cancer prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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CAMKK1 rs7214723 single nucleotide polymorphism lung cancer prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Haorui Zhang Bocen Chen Zixiu Zou Jian Feng Yutao Li Yi Wang Xing He Chang Xu Haijian Wang Shicheng Guo Li Jin Li Jin Qiang Li Jiucun Wang Jiucun Wang Man Xiao Feng Li Junjie Wu Junjie Wu Junjie Wu Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer |
| description |
BackgroundThe 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 Ca2+/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer.MethodsGenomic 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.ResultsThe 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.ConclusionsCAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer. |
| format |
article |
| author |
Haorui Zhang Bocen Chen Zixiu Zou Jian Feng Yutao Li Yi Wang Xing He Chang Xu Haijian Wang Shicheng Guo Li Jin Li Jin Qiang Li Jiucun Wang Jiucun Wang Man Xiao Feng Li Junjie Wu Junjie Wu Junjie Wu |
| author_facet |
Haorui Zhang Bocen Chen Zixiu Zou Jian Feng Yutao Li Yi Wang Xing He Chang Xu Haijian Wang Shicheng Guo Li Jin Li Jin Qiang Li Jiucun Wang Jiucun Wang Man Xiao Feng Li Junjie Wu Junjie Wu Junjie Wu |
| author_sort |
Haorui Zhang |
| title |
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_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_sort |
associations between camkk1 polymorphism rs7214723 and the prognosis of patients with lung cancer |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/9ae897a769dd4b8995dc1c624a2f05c7 |
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