Yan Xiaopeng, Shao Cong, Chen Chuang, Chen Jun, Gu Shen, Huang Luoshun, Fu Xu, Zhao Hui, Qiu Yudong
Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Dig Dis Sci. 2017 Feb;62(2):407-417. doi: 10.1007/s10620-016-4408-7. Epub 2017 Jan 5.
Gene data on infiltrative hepatocellular carcinoma (iHCC) are still unknown.
This study aims to identify the gene expression signature of iHCC compared with single nodular (SN)-type HCC according to the gross classification.
The whole-exome sequencing was performed in six matched HCC tumor/normal pairs (three infiltrative type and three single nodular type) from six patients who received curative hepatectomy. Subsequent validation using Sanger sequencing and real-time PCR was performed in 30 HCC tumor samples (15 infiltrative type and 15 single nodular type).
Following whole-exome sequencing, Sanger sequencing, and bioinformatics analysis, it revealed significant difference of iHCC from SN-type HCC in gene patterns. Particularly, a typical growth factor receptor tyrosine kinase FGFR3 was predominantly mutated in iHCC. One nonsynonymous variant c.G285T (p.Q95H) and five additional mutations (c.G938A:p.G313D, c.G1291A:p.A431T, c.C1355G:p.T452R, c.C1377T:p.L459L, and c.A1445T:p.E482V) were investigated by whole-exome and Sanger sequencing, respectively. Immunohistochemical studies confirmed the specific expression of FGFR3 in iHCC samples.
Our studies indicated that FGFR3 may be a candidate oncogene in tumor progression and a promising therapeutic target in iHCC patients who had early recurrence.
浸润性肝细胞癌（iHCC）的基因数据仍不清楚。
本研究旨在根据大体分类确定与单结节（SN）型肝癌相比iHCC的基因表达特征。
对6例接受根治性肝切除术患者的6对匹配的肝癌肿瘤/正常组织（3例浸润型和3例单结节型）进行全外显子组测序。随后在30例肝癌肿瘤样本（15例浸润型和15例单结节型）中使用桑格测序和实时PCR进行验证。
经过全外显子组测序、桑格测序和生物信息学分析，发现iHCC与SN型肝癌在基因模式上存在显著差异。特别是，典型的生长因子受体酪氨酸激酶FGFR3在iHCC中主要发生突变。分别通过全外显子组测序和桑格测序研究了一个非同义变体c.G285T（p.Q95H）和另外五个突变（c.G938A:p.G313D、c.G1291A:p.A431T、c.C1355G:p.T452R、c.C1377T:p.L459L和c.A1445T:p.E482V）。免疫组织化学研究证实了FGFR3在iHCC样本中的特异性表达。
我们的研究表明，FGFR3可能是肿瘤进展中的候选癌基因，也是早期复发的iHCC患者有前景的治疗靶点。
