AUTHOR=Liao Xiaoli , Chen Junming , Luo DongCheng , Luo Baohua , Huang Wenfeng , Xie Weimin 

TITLE=Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 28 - 2022

YEAR=2023

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610808

DOI=10.3389/pore.2022.1610808

ISSN=1532-2807

ABSTRACT=Aiming to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC), we constructed a MALAT1 protein-protein interaction network and a network of competing endogenous RNAs (ceRNAs) using the STRING and StarBase database. Correlations between genes in these networks and survival of patients with HCC was analyzed using the GEPIA2 database. More relationships between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test. Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with two gene mutations leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for low, while the corresponding median OS was 40.5 and 78.3 months.  In subgroup analysis, patients overexpressed MALAT1 had significantly shorter PFS and OS of with vascular invasion, cirrhosis, and HBsAg positive or AFP positive.  Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661 - 0.731.  In conclusion, MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.