Gong Yang, Zhao Wenjing, Jia Qiong, Dai Jiali, Chen Nan, Chen Yuetong, Gu Dongying, Huo Xinying, Chen Jinfei
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Cancer Center, Taikang Xianlin Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, People's Republic of China.
Pharmgenomics Pers Med. 2020 Aug 19;13:345-352. doi: 10.2147/PGPM.S258761. eCollection 2020.
IKBKB/IKKβ, as the core catalytic subunit of IκB kinase complex, participates in mediation of the classical NF-κB pathway, which has been linked to inflammation and tumorigenesis. Previous studies have shown that single nucleotide polymorphisms in IKBKB have been related to gastric cancer, but how they associate to the clinical outcome is not yet clear. In this study, we retrospectively investigated the associations between single nucleotide polymorphisms located in IKBKB and gastric cancer survival.
IKBKB rs2272736 was genotyped in 1210 patients with primary gastric cancer in a Han Chinese population, and the relationships between rs2272736 and overall survival were evaluated. We conducted Cox proportional hazards regression, which was performed to estimate the effects of single nucleotide polymorphisms on the overall survival of patients, adjusted for potential confounding variables.
We found that patients with rs2272736 A allele in IKBKB had significantly prolonged overall survival time compared to those with the G allele (HR = 0.83, 95% CI = 0.68-1.00, = 0.050). In addition, AA genotype was demonstrated to have reduced risk of death for gastric cancer compared with that associated with the GG/GA genotypes, which was more common in patients with cardiac carcinoma, well-differentiated and moderately differentiated tumors, TNM Ⅰ/Ⅱ stages and intestinal type.
Our findings have shown that single nucleotide polymorphism rs2272736 in IKBKB may be a promising prognostic biomarker which should promote personalized treatment.
IKBKB/IKKβ作为IκB激酶复合体的核心催化亚基,参与经典NF-κB信号通路的介导,该通路与炎症和肿瘤发生有关。既往研究表明,IKBKB中的单核苷酸多态性与胃癌相关,但它们与临床结局的关联尚不清楚。在本研究中,我们回顾性调查了IKBKB中存在的单核苷酸多态性与胃癌生存之间的关联。
对1210例汉族原发性胃癌患者的IKBKB rs2272736进行基因分型,并评估rs2272736与总生存的关系。我们进行了Cox比例风险回归分析,以估计单核苷酸多态性对患者总生存的影响,并对潜在的混杂变量进行校正。
我们发现,与携带G等位基因的患者相比,携带IKBKB rs2272736 A等位基因的患者总生存时间显著延长(HR = 0.83,95%CI = 0.68-1.00,P = 0.050)。此外,与GG/GA基因型相比,AA基因型的胃癌死亡风险降低,GG/GA基因型在贲门癌、高分化和中分化肿瘤、TNMⅠ/Ⅱ期和肠型患者中更常见。
我们的研究结果表明,IKBKB中的单核苷酸多态性rs2272736可能是一种有前景的预后生物标志物,应推动个性化治疗。