Zeng Jiajia, Han Linyu, Wang Teng, Huang Linying, Zheng Yanxiu, Zhang Nasha, Li Ziqiang, Yang Ming
Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, People's Republic of China.
Pharmgenomics Pers Med. 2023 Mar 18;16:229-238. doi: 10.2147/PGPM.S402115. eCollection 2023.
Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE.
In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes ( and ) in two independent TACE patient cohorts.
We found that rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs.
Our findings highlighted the value of polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.
经动脉化疗栓塞术（TACE）是不可切除肝细胞癌（HCC）常用的治疗方法，然而不同接受TACE治疗的HCC患者预后各异，这可能是由于基因变异和诸如RNA编辑等表观遗传变化导致的HCC肿瘤异质性所致。HCC中存在RNA腺苷到肌苷（A到I）编辑失调，且RNA编辑基因参与表观遗传过程。RNA编辑基因的基因变异如何影响接受TACE治疗的HCC病例的预后仍不清楚。
在本研究中，我们在两个独立的TACE患者队列中检测了四个RNA编辑基因（和）的28个潜在功能性单核苷酸多态性（SNP）。
我们发现rs1051367和rs2253763多态性在两个队列中均与接受TACE治疗的HCC病例的预后显著相关。在HCC细胞中，3'-非翻译区的rs2253763 C到T变化减弱了其与miR-542-3p的结合，并等位基因特异性地提高了水平。与此一致，携带rs2253763 C等位基因的患者在癌组织中的表达降低，与携带T等位基因的个体相比，TACE治疗后的生存期明显缩短。异位显著增强了常见TACE化疗药物之一奥沙利铂的疗效。
我们的研究结果突出了多态性作为HCC患者TACE治疗预后标志物的价值。值得注意的是，我们的研究结果表明，针对ADARB1酶可能是与TACE联合用于HCC病例的一种有前景的治疗策略。
