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...
| Main Authors: | , , , , , , , , , , , , , , , |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.757484/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T23:28:23Z |
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| id | doaj.art-9ae897a769dd4b8995dc1c624a2f05c7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T23:28:23Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-9ae897a769dd4b8995dc1c624a2f05c72022-12-21T19:23:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.757484757484Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung CancerHaorui Zhang0Bocen Chen1Zixiu Zou2Jian Feng3Yutao Li4Yi Wang5Xing He6Chang Xu7Haijian Wang8Shicheng Guo9Li Jin10Li Jin11Qiang Li12Jiucun Wang13Jiucun Wang14Man Xiao15Feng Li16Junjie Wu17Junjie Wu18Junjie Wu19Department of Ophthalmology, Changhai Hospital, Navy Military Medical University, Shanghai, ChinaDepartment of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Urology, Navy Military Medical University Affiliated Changhai Hospital, Shanghai, ChinaClinical College, Xiangnan University, Chenzhou, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaHuman Phenome Institute, Fudan University, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaHuman Phenome Institute, Fudan University, Shanghai, ChinaDepartment of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China0Department of Respiratory Disease, Shanghai Public Health Clinical Center, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China1Department of Infectious Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China2Department of Respiratory and Critical Care Medicine, Changhai Hospital, Navy Military Medical University, Shanghai, ChinaBackgroundThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.757484/fullCAMKK1rs7214723single nucleotide polymorphismlung cancerprognosis |
| spellingShingle | 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 Frontiers in Oncology CAMKK1 rs7214723 single nucleotide polymorphism lung cancer prognosis |
| 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 | CAMKK1 rs7214723 single nucleotide polymorphism lung cancer prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.757484/full |
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