外动力蛋白臂对接复合物亚基 2 多态性 rs7893462 调节肝细胞癌易感性，并可作为乙型肝炎病毒相关肝细胞癌肝切除术后总生存期的生物标志物：一项具有长期随访的队列研究。
Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up.
机构信息
Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
出版信息
World J Surg Oncol. 2023 Oct 13;21(1):322. doi: 10.1186/s12957-023-03205-4.
BACKGROUND
Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported.
METHODS
We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi.
RESULTS
Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival.
CONCLUSION
The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.
背景
先前的研究表明，外动力蛋白臂对接复合物亚基 2（ODAD2）的遗传变异与原发性纤毛运动障碍和结直肠癌密切相关，但 ODAD2 遗传变异与肝细胞癌（HCC）的关联尚未报道。
方法
本研究纳入了 80 名健康对照者和 468 名广西乙型肝炎病毒（HBV）相关 HCC 患者。采用病例对照研究方法，探讨不同 ODAD2-rs7893462 基因型与肝癌发生的关系。采用综合生存分析探讨 rs7893462 与广西 HBV 相关 HCC 预后的关系。
结果
通过病例对照研究，我们观察到携带 rs7893462 G 等位基因的患者肝癌发生的易感性明显增加（比值比=1.712，95%置信区间=1.032-2.839，P=0.037）。我们发现 rs7893462 的三种不同基因型之间存在显著的预后差异。列线图分析提示，rs7893462 多态性对 HBV 相关 HCC 预后的贡献仅次于 BCLC 分期。分层生存分析提示 rs7893462 的 AG 基因型是 HBV 相关 HCC 的独立预后危险因素。联合效应生存分析还观察到 rs7893462 的 AG 基因型与临床参数相结合，可以更准确地识别具有不同预后结局的 HBV 相关 HCC 患者，并且在 HBV 相关 HCC 生存中，rs7893462 也被观察到独立于临床因素。
结论
ODAD2-rs7893462 多态性可作为 HBV 相关 HCC 总生存的独立预后指标，与肝癌易感性显著相关。
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