AUTHOR=Cui Zhongyuan , Wang Jielong , Chen Gang , Li Dongliang , Cheng Bianqiao , Lai Yanhua , Wu Zhixian 

TITLE=The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1081510

DOI=10.3389/fonc.2022.1081510

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Patients with hepatocellular carcinoma (HCC) have poor prognosis, especially in advanced stages. Targeted therapy is the main treatment for advanced HCC patients, but the optimal targets for HCC remain poorly understood. The main purpose of this study was to identify potential novel prognostic markers and therapeutic targets.</p></sec><sec><title>Methods</title><p>Firstly, differentially expressed genes (DEGs) in HCC were identified from the Gene Expression Omnibus (GEO) database. The expression, significance in prognosis, and potential mechanisms of DEGs were analyzed using GEPIA, TIMER, HPA, Kaplan Meier Plotter, CBioPortal, miRWalk, TargetScan, and ENCORI databases. Immunohistochemical staining was used to determine the protein expression levels of potential candidate genes.</p></sec><sec><title>Results</title><p>The mRNA levels of <italic>MND1</italic>, <italic>STXBP6</italic>, and <italic>CLGN</italic> were significantly increased in HCC (<italic>p</italic>&lt; 0.01). HCC patients with elevated <italic>CLGN</italic> mRNA levels had poorer overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS) (<italic>p</italic> &lt; 0.05). Higher <italic>MND1</italic> mRNA levels significantly correlated with poorer DFS in HCC patients (<italic>p</italic>&lt; 0.05). However, there was no significant correlation between <italic>STXBP6</italic> expression and prognosis of HCC (<italic>p</italic>&gt; 0.05). Further analysis revealed that patients with elevated <italic>CLGN</italic> mRNA expression in advanced pathology stages had poorer prognosis (<italic>p</italic>&lt; 0.01). In addition, CLGN protein levels were elevated in HCC compared to their levels in normal tissues. The mRNA levels of <italic>CLGN</italic> had no significant correlation with the abundance of six common tumor infiltrating lymphocytes in HCC (COR &lt; 0.5). Moreover, the mutation rate of <italic>CLGN</italic> was less than 1% in HCC patients (10/1089). Finally, the expression level of hsa-miR-194-3p in HCC was significantly lower than that in normal tissues (<italic>p</italic> &lt; 0.05), and prognosis of HCC with low expression of hsa-miR-194 was poor (<italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>The upregulation of <italic>CLGN</italic> in HCC is significantly associated with poor patient prognosis, especially in the advanced stages, and may be regulated by hsa-miR-194-3p. These findings suggest that <italic>CLGN</italic> may be closely related to the progression of HCC, and is a potential therapeutic target and prognostic indicator for patients with advanced HCC.</p></sec>