The potential, analysis and prospect of ctDNA sequencing in hepatocellular carcinoma.
The potential, analysis and prospect of ctDNA sequencing in hepatocellular carcinoma.
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肝细胞癌ctDNA测序的潜力、分析与展望。
DOI：
10.7717/peerj.13473
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发表时间：
2022
期刊：
影响因子：
2.7
通讯作者：
Zuo, JianHong
中科院分区：
文献类型：
--
作者：
Ding, Yubo;Yao, Jingwei;Wen, Meiling;Liu, Xiong;Huang, Jialu;Zhang, Minghui;Zhang, Yu;Lv, Yufan;Xie, Zhuoyi;Zuo, JianHong
肝细胞癌（HCC）的基因组图谱是复杂的。为了探讨循环肿瘤细胞DNA（ctDNA）是否可以作为测序的基础，并利用ctDNA寻找肿瘤相关生物标志物，我们对肝癌患者ctDNA突变基因进行了测序分析。我们使用下一代靶向测序技术来识别肝癌患者的突变。对10例原发性肝癌（8例原发性肝癌，2例继发性肝癌）患者的ctDNA进行测序。我们使用SAMtools检测和筛选单核苷酸多态性（SNP）和插入缺失突变（INDEL），并使用ANNOVAR注释检测到的突变的结构和功能。使用美国医学遗传学和基因组学学院（ACMG）指南进行致病和可能致病基因的筛选。使用大卫数据库进行致病基因和可能致病基因的GO分析和KEGG分析，使用STRING数据库进行致病基因和可能致病基因的蛋白质-蛋白质相互作用网络分析。然后利用Kaplan-Meier秩和检验数据库、GEPIA数据库和HPA数据库分析致病基因和可能致病基因与肝癌患者的关系。对10个肝癌ctDNA样本中的560个癌症相关基因进行靶向捕获和深度测序，发现了8，950个单核苷酸变异（SNV）突变和70个INDELS。最常见的突变基因是PDE 4DIP，其次是SYNE 1、KMT 2C、PKHD 1和FN 1。我们将这些结果与COSMIC数据库进行了比较，并确定ctDNA可用于测序。根据ACMG指南，我们在10例HCC患者的外显子和剪接区的39个基因中确定了54个致病和可能致病的突变，并进行了GO分析，KEGG分析和PPI网络分析。通过进一步分析，确定了4个与肝癌预后显著相关的基因。在这项研究中，我们的发现表明ctDNA可以用于测序。我们的研究结果为中国肝癌患者的遗传变异定位提供了一些分子数据，丰富了对肝癌发病机制的认识，为肝癌患者的诊断和预后提供了新的思路。
The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein–protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan–Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients.
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影响因子：
4.6
作者：
Kim SA;Cho EJ;Lee S;Cho YY;Kim B;Yoon JH;Park T
通讯作者：
Park T
RECQL4表达上调预示肝细胞癌预后不良
影响因子：
2.9
作者：
Li J;Jin J;Liao M;Dang W;Chen X;Wu Y;Liao W
通讯作者：
Liao W
DOI：
10.1083/jcb.201701024
发表时间：
2017-10-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yang C;Wu J;de Heus C;Grigoriev I;Liv N;Yao Y;Smal I;Meijering E;Klumperman J;Qi RZ;Akhmanova A
通讯作者：
Akhmanova A
影响因子：
8
作者：
Kim, Seok-Hwan;Moon, Deok-Bog;Lee, Sung-Gyu
通讯作者：
Lee, Sung-Gyu
影响因子：
2
作者：
Liu B;Ding Y;Li P;Wang T;He S;Jia Z;Yang J
通讯作者：
Yang J