Genomic Analysis of Vascular Invasion in HCC Reveals Molecular Drivers and Predictive Biomarkers

Autor: Renumathy Dhanasekaran, Nishita Kothary, Maya Krishnan, Jun Yin, Sharon J. Pitteri, Vinodhini Arjunan, Dean W. Felsher, Jangho Park, Anand Rajan Kd, Mindie H. Nguyen, Abel Bermudez, Nam S. Hoang, Fernando Jose Garcia Marques, Olivia A. Girvan
Rok vydání: 2021
Předmět:
Zdroj: Hepatology
ISSN: 1527-3350
0270-9139
Popis: BACKGROUND AND AIMS Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. APPROACH AND RESULTS To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC-driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10-11 ; human FN1, P = 1.5 × 10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P
Databáze: OpenAIRE
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