Deep sequencing and comprehensive expression analysis identifies several molecules potentially related to human poorly differentiated hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) that is graded histologically as poorly differentiated has a high recurrence, metastasis and poor prognosis. We sought to determine the regulatory mechanisms of HCC tumorigenesis and to identify molecules closely related to poorly differentiated HCC. High‐throughput sequencing was used to construct microRNA (miRNA) and mRNA expression profiles for poorly differentiated HCC tissues and adjacent tissues. Network analysis was carried out to study miRNA–target interactions. Integrating the miRNA and mRNA data of HCC with four tumor grades from The Cancer Genome Atlas (TCGA) portal enabled the identification of potential closely related molecules for early diagnosis of poorly differentiated HCC. Electronic validation of RNA‐seq data and survival analysis was also performed. In total, 1051 differentially expressed genes and 165 differentially expressed miRNAs were identified between HCC tumor and paired non‐tumorous tissue. Based on 3718 miRNA–target interactions, we established an miRNA–target interaction network; the target genes were mainly involved in bile acid biosynthesis and bile secretion. Integrating expression data of HCC from TCGA indicated that two proteins, TM4SF1 and ANXA2, are convincing indicators for initial diagnosis of poorly differentiated HCC. According to the survival analysis, three proteins, ANXA2, C8orf33 and IGF2BP3, were identified as being associated with the survival time of HCC patients. Moreover, we suggest that hsa‐miR‐1180 may be an effective biomarker for poorly differentiated HCC. Three molecules, TM4SF1, ANXA2 and C8orf33, are potential biomarkers for distinguishing poorly differentiated from well‐differentiated HCC.

LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma

“…IGF2BP3, a RNA‐binding protein, has been reported to be associated with HCC progression . Thus, we aimed to determine whether IGF2BP3 interacted with LINC00467 (or TRAF5) in HCC.…”

“…IGF2BP3, a RNA-binding protein, has been reported to be associated with HCC progression. 18,19 Thus, we aimed to determine whether IGF2BP3 interacted with LINC00467 (or TRAF5) in HCC. To verify the speculation, starBase (http://starbase.sysu.edu.cn) was utilized, which indicated that LINC00467 could possibly bind with IGF2BP3 ( Figure 3A).…”

Identification of biomarkers for Barcelona Clinic Liver Cancer staging and overall survival of patients with hepatocellular carcinoma

“…Among these 13 hub genes, 4 ( C8ORF33 , STIP1 , Hsp90AB1 and PRKDC ) have been implicated in HCC behaviour by previous studies [ 28 – 31 ]. C8ORF33 has been associated with OS in HCC patients and could be used to distinguish poorly differentiated from well differentiated HCCs [ 28 ]. STIP1 acts as an adaptor protein that coordinates functions of HSP70 and HSP90 in protein folding, and as a secretory protein that regulates malignant cell growth.…”

SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β‐catenin signaling pathway

“…Hepatocellular carcinoma (HCC) is one of the most common malignancies, with high incidence and mortality, especially among East Asian and sub‐Saharan African populations . Unfortunately, the efficacy of current therapeutic strategies for HCC is unsatisfactory , leading to poor prognosis and high recurrence rate after surgical resection of primary tumors .…”