多态性rs7214723与肺癌患者预后的关联
Associations Between Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer.
作者信息
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
机构信息
Department of Ophthalmology, Changhai Hospital, Navy Military Medical University, Shanghai, China.
Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, China.
出版信息
Front Oncol. 2021 Nov 19;11:757484. doi: 10.3389/fonc.2021.757484. eCollection 2021.
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/calmodulin-dependent protein kinase kinase 1 () 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 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 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 rs7214723 recessive CC genotype conferred significantly better overall survival (CC . TT + TC: adjusted hazard ratio = 0.78, 95% confidence interval [CI], 0.61-1.00, = 0.049) than the TT + TC genotypes. Stratified analysis showed that the 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 . TT + TC: adjusted hazard ratio = 0.59, 95% CI, 0.37-0.93, = 0.024) and patients with squamous cell carcinoma (CC . TT + TC: adjusted hazard ratio = 0.65, 95% CI, 0.44-0.98, = 0.038). Remarkably, CRISPR/Cas9-guided single nucleotide editing demonstrated that rs7214723 T > C mutation significantly inhibits cell proliferation and migration and promotes cell apoptosis.
CONCLUSIONS
SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer.
背景
中国肺癌患者的5年生存率低于20%，预测其预后具有挑战性。我们研究了钙/钙调蛋白依赖性蛋白激酶激酶1（）基因中常见的非同义单核苷酸多态性（SNP）rs7214723与肺癌患者预后之间的关联。
方法
从长海医院（n = 536）和泰州卫生科学研究所（n = 352）招募的839例肺癌患者的血液样本中提取基因组DNA，并使用SNPscan技术进行基因分型。使用针对多个潜在混杂因素进行调整的多变量Cox比例风险模型分析患者预后与的基因型数据之间的关联。使用CRISPR/Cas9基因编辑系统在A549和NCI-H358细胞的rs7214723中引入点突变。随后，使用细胞计数试剂盒-8和划痕试验评估细胞增殖和迁移能力。使用Annexin V-FITC凋亡检测试剂盒检测细胞凋亡。
结果
rs7214723隐性CC基因型的总生存率显著高于TT + TC基因型（CC . TT + TC：调整后的风险比 = 0.78，95%置信区间[CI]，0.61 - 1.00， = 0.049）。分层分析表明，与TT和TT + TC基因型相比，rs7214723 CC基因型和隐性CC基因型在男性、有吸烟史或患有III + IV期癌症的患者中死亡风险显著降低。相对于TT + TC基因型，rs7214723隐性CC基因型在年龄<60岁的患者（CC . TT + TC：调整后的风险比 = 0.59，95% CI，0.37 - 0.93， = 0.024）和鳞状细胞癌患者（CC . TT + TC：调整后的风险比 = 0.65，95% CI，0.44 - 0.98， = 0.038）中也与死亡风险降低相关。值得注意的是，CRISPR/Cas9引导的单核苷酸编辑表明，rs7214723 T > C突变显著抑制细胞增殖和迁移并促进细胞凋亡。
结论
SNP rs7214723可能是肺癌患者死亡风险的一个重要预后因素。
Zotero 插件