Research Paper Volume 14, Issue 4 pp 1743—1766
THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation
- 1 The Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
- 2 The Department of Tuberculosis, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
- 3 Laboratory of Infection and Immunity, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
Received: January 30, 2021 Accepted: January 17, 2022 Published: February 23, 2022https://doi.org/10.18632/aging.203900
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Copyright: © 2022 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.
HCC: hepatocellular carcinoma; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; DEGs: differentially expressed genes; WGCNA: Weighted Gene Co-expression Network Analysis; PPI: protein-protein interaction; THRSP: thyroid hormone-responsive; LIHC: liver hepatocellular carcinoma; STRING: search tool for the retrieval of interacting genes; MCC: maximal clique centrality; MCODE: molecular complex detection; OS: overall survival; GEPIA: Gene Expression Profiling Analysis; FDR: false discovery rate; qRT-PCR: quantitative real-time polymerase chain reaction; TIMER: Tumor Immune Estimation Resource; siRNA: small interfering RNA; DMSO: Dimethyl sulfoxide; NC group: normal control group; PBS: phosphate-buffered saline; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; PVDF: polyvinylidene fluoride; TBST: tris-buffer saline tween; ECL: enhanced chemiluminescence.