Abstract
BACKGROUND: The mechanism of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) has been widely studied, and numerous diagnostic and prognostic biomarkers for HCC with PVTT have been identified. We aimed to evaluate the extent to which these biomarkers may aid the personalized precision therapy of HCC with PVTT. METHODS: Matched tissue specimens [primary HCC tumor (PT), adjacent normal (N) liver, and PVTT tissues] were acquired from 3 Chinese HCC patients who underwent surgery at Sun Yat-sen University Cancer Centre between 2019 and 2020. Ribonucleic acid (RNA) sequencing was performed on the 9 tissue samples. GFOLD (generalized fold change) algorithm was used to analyze the differently expressed genes (DEGs) between the PVTT, PT, and normal tissues from each patient. Genes with a P<0.01 and a |GFOLD value| >1 were identified as having significantly different expression. RESULTS: In total, 3,543, 32,472, and 12,901 tumorigenesis-associated genes, and 2,919, 17,679, and 14,825 metastasis-associated genes, were detected in Patient 1 (P1), Patient 2 (P2), and Patient 3 (P3), respectively. We analyzed the expression levels of genes associated with hypoxia, macrophage recruitment and cancer stem cells (CSCs). The results showed that hypoxia and CSCs may have contributed to tumorigenesis but not to metastasis in P1. We also found the hypoxia microenvironment played an important role in tumorigenesis and metastasis in P2, and CSCs may have contributed to metastasis. Additionally, we found that CSCs played critical roles in metastasis but not in tumorigenesis in P3. The results also showed that the long non-coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was greatly overexpressed in the PTs and PVTT in all 3 patients, and Heart and Neural Crest Derivatives Expressed 2-antisense RNA 1 (HAND2-AS1) was downregulated in PVTT compared with PTs in all 3 patients. Thus, MALAT1 and HAND2-AS1 may be robust biomarkers for metastasis in HCC patients with PVTT. CONCLUSIONS: Tumor-associated macrophages (TAMs)-targeted immunotherapy is a promising therapy for HCC patients with PVTT. LncRNAs MALAT1, and HAND2-AS1 may be promising targets for HCC therapy.