Xiaopeng Yan1, Cong Shao1, Chuang Chen2,3, Jun Chen4, Shen Gu1, Luoshun Huang1, Xu Fu1, Hui Zhao2, Yudong Qiu5. 1. Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China. 2. Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. 3. Department of General Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Second People's Hospital of Huai'an City, Huai'an, China. 4. Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. 5. Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China. yudongqiu510@163.com.
Abstract
BACKGROUND: Gene data on infiltrative hepatocellular carcinoma (iHCC) are still unknown. AIMS: This study aims to identify the gene expression signature of iHCC compared with single nodular (SN)-type HCC according to the gross classification. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
BACKGROUND: Gene data on infiltrative hepatocellular carcinoma (iHCC) are still unknown. AIMS: This study aims to identify the gene expression signature of iHCC compared with single nodular (SN)-type HCC according to the gross classification. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
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