新疆地区原发性肝癌肿瘤同时性转移基因差异表达

目的：研究新疆地区原发性肝癌肿瘤同时性转移原发灶和转移灶的基因差异表达。方法：选取新疆医科大学第一附属医院2018年1月 ~ 2021年5月收治的首次出现同时性转移的原发性肝癌患者21例,采用下一代测序技术（NGS）研究其原发灶和转移灶中突变基因的表达,以及所涉及的通路和药物作用靶点,分析其突变基因与临床特征的关系;并用Kaplan-Meier单因素生存分析统计患者基因突变与临床特征及总生存期间的相关性。结果：原发性肝癌标本中原发灶和转移灶共同显示出突变率最高的10种基因：MUC16（43%）、TTN（36%）、ZAN（29%）、MYO18B（29%）、DNAH7（29%）、DNAH10（29%）、DMLX2（29%）、DCC（29%）、CSMD1（29%）、CDLSR2（29%）,转移灶和原发灶突变基因差异无统计学意义（P ＞ 0.05）,且基因变异的分类主要为错义突变,以单核苷酸多态性（SNP）最多见。在碱基突变的统计中,C ＞ A替换发生率最高,C ＞ T替换的发生频率次之。原发性肝癌患者TTN基因突变与性别、族别、分化程度有关（P ＜ 0.05）;MYO18B基因突变与族别有关（P ＜ 0.05）;TTN基因突变是原发性肝癌患者预后的独立预测基因;共筛选出10个原发灶和转移灶中突变基因的共同药物作用靶点,分别为可成药基因组、丝氨酸/苏氨酸激酶、离子通道、肿瘤抑制因子、酪氨酸激酶、DNA修复因子、复杂转录因子、转录因子结合位点、肿瘤治疗靶点基因组、ABC转运体。结论：原发性肝癌同时性转移异质性不明显。本研究筛选出原发性肝癌少见基因突变、与临床预后相关的基因突变以及药物作用靶点和基因突变所涉及的通路,为原发性肝癌的诊断、潜在的治疗靶点及相关的分子机制研究提供参考。

Differential Gene Expression in Simultaneous Metastasis of Primary Hepatocellular Carcinoma in Xinjiang

Objective: To study the differential expression of genes in simultaneous metastasis of primary and metastatic foci of primary hepatocellular carcinoma in Xinjiang. Methods: A total of 21 patients with primary liver cancer with local recurrence treated in the First Affiliated Hospital of Xinjiang Medical University from 2018 Jan to 2021 May were selected to study the expression of mutant genes, pathways and drug targets in the primary and metastatic foci by next-generation sequencing (NGS). Statistical analysis was performed to analyze the relationship between mutated genes and clinical characteristics. Kaplan-Meier univariate survival analysis was used to calculate the correlation between gene mutations and clinical features and overall survival (OS) (P < 0.05). Results: The ten genes with the highest mutation rates were MUC16 (43%), TTN (36%), ZAN (29%), MYO18B (29%), DNAH7 (29%), DNAH10 (29%), DMLX2 (29%), DCC (29%), CSMD1 (29%) and CDLSR2 (29%). There was no significant difference in mutant genes between metastatic and primary foci (P > 0.05). The classes of gene variation were mainly missense mutation, and single nucleotide polymorphism (SNP) was the most common. In the statistics of base mutation, the incidence of C > A substitution was the highest, and that of C > T substitution was the second. TTN gene mutation in patients with primary hepatocellular carcinoma was related to sex, ethnic group, degree of differentiation (P < 0.05), and MYO18B gene mutation was related to ethnic group (P < 0.05). TTN gene mutation was an independent predictor of prognosis in patients with primary hepatocellular carcinoma. Ten common drug targets of mutant genes in primary and metastatic foci were also screened, which were druggable genome, serine threonine kinase, ion channel, tumor suppressor, tyrosine kinase, DNA repair, transcription factor complex, transcription factor binding, clinically actionable and ABC transporter. Conclusion: The heterogeneity of primary hepatocellular carcinoma is not obvious. Rare gene mutations in primary hepatocellular carcinoma, gene mutations related to clinical prognosis, drug targets and pathways involved in gene mutations screened here provide clues for diagnosis, potential therapeutic targets and related molecular mechanisms of primary hepatocellular carcinoma.