Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma.
Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma.
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癌症基因组改变可能是预测肝细胞癌微血管侵袭和早期复发的潜在生物标志物
DOI：
10.3389/fonc.2022.783109
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发表时间：
2022
影响因子：
4.7
通讯作者：
Ying B
中科院分区：
文献类型：
--
作者：
Xin Z;Li J;Zhang H;Zhou Y;Song J;Chen P;Bai L;Chen H;Zhou J;Chen J;Ying B
微血管侵犯（MVI）是肝细胞癌（HCC）术后复发率高、生存率低的主要原因。然而，很难预测术前MVI状态。在这项研究中，我们专注于癌症基因组改变，全面探索潜在的MVI和早期复发的生物标志物，并为HCC侵袭和转移的机制提供线索。最终入选了41例最初怀疑患有HCC并接受肝切除术的患者。利用1，021个基因组对患者术前血浆和手术新鲜肿瘤组织中的基因组改变进行高通量靶向测序。无MVI的HCC患者RFS较MVI患者长（p < 0.0001）。KEAP 1、TP 53、HIST 1H 3D、NFKBIA、PIK 3CB和WRN等基因突变发生率在MVI和早期复发患者中均高于其对应者。MVI组Rap 1和Ras信号通路的改变率显著高于NMVI组（p < 0.05），在早期复发/未复发的比较中也有类似的差异趋势。MVI患者循环肿瘤DNA（ctDNA）的最大变异等位基因频率（VAF）在统计学上高于NMVI患者（0.038 vs. 0.012，p = 0.0048）。截止值为0.018时，ctDNA最大VAF可能预测MVI的存在，AUC为0.85（95% CI 0.693-0.998，p = 0.0062）。整合包含特定突变基因的面板和ctDNA最大VAF用于预测MVI和HCC的早期复发可能实现更好的性能。
High recurrence incidence and poor survival after hepatectomy are enormous threats to hepatocellular carcinoma (HCC) patients, which can be caused by microvascular invasion (MVI). However, it is difficult to predict preoperative MVI status. In this study, we focus on cancer genomic alterations to comprehensively explore potential MVI and early recurrence biomarkers and provide clues to the mechanisms of HCC invasion and metastasis. Forty-one patients with initially suspected HCC who were undergoing hepatectomy were finally enrolled. High-throughput targeted sequencing was performed on genomic alterations in their preoperative plasma and surgical fresh tumor tissues utilizing the 1,021-gene panel. HCC patients without MVI had longer RFS than MVI ones (p < 0.0001). The mutant incidence of genes like KEAP1, TP53, HIST1H3D, NFKBIA, PIK3CB, and WRN was higher in both MVI and early-recurrence patients than their counterparts. Besides, the alteration rates of Rap1 and Ras signaling pathways were significantly higher in MVI patients than NMVI ones (p < 0.05), and a similar trend of differences was also found in early-recurrence/non-recurrence comparison. The maximal variant allele frequency (VAF) of circulating tumor DNA (ctDNA) was statistically higher in MVI patients than NMVI ones (0.038 vs. 0.012, p = 0.0048). With the cutoff value of 0.018, ctDNA maximal VAF could potentially predict the presence of MVI with an AUC of 0.85 (95% CI 0.693–0.998, p = 0.0062). The integration of a panel containing specific mutated genes and ctDNA maximal VAF for predicting MVI and early recurrence of HCC may achieve better performance.
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癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
使用微滴式数字 PCR 检测肝细胞癌患者的循环肿瘤 DNA 是可行的，并反映了瘤内异质性
影响因子：
3.9
作者：
Huang A;Zhang X;Zhou SL;Cao Y;Huang XW;Fan J;Yang XR;Zhou J
通讯作者：
Zhou J
影响因子：
4.7
作者：
Looi CK;Hii LW;Ngai SC;Leong CO;Mai CW
通讯作者：
Mai CW
影响因子：
3.8
作者：
Du M;Chen L;Zhao J;Tian F;Zeng H;Tan Y;Sun H;Zhou J;Ji Y
通讯作者：
Ji Y
DOI：
10.1016/j.jamcollsurg.2005.10.005
发表时间：
2006-02-01
影响因子：
5.2
作者：
Shah, SA;Greig, PD;Vollmer, CM
通讯作者：
Vollmer, CM