Introduction: Hepatocellular carcinoma (HCC) continues to be a cancer with rising incidence, high mortality, and recurrence rate. The therapeutic effects on HCC are not satisfactory currently. Epidermal growth factor receptor (EGFR) is an important factor, while anti-EGFR agencies have not shown ideal results in HCC.
Materials and Methods: We tested efficacy of nimotuzumab and EGFR expression on cell surface in six HCC cell lines (Hep 3B2.1– 7, Li-7, PLC/PRF/5, SK-HEP-1, SNU-182, and SNU-387). Then, we analyzed RNA sequences of every cell line and performed a bioinformatic analysis. Differentially expressed genes (DEGs) were analyzed. The data, TCGA-LIHC from The Cancer Genome Atlas (TCGA) and GSE102079 from Gene Expression Omnibus (GEO), were used to analyse DEGs of Hoshida subclass.
Results: Hep 3B2.1– 7 and PLC/PRF/5 were sensitive to nimotuzumab whereas Li-7, SK-HEP-1, SNU-182, and SNU-387 cell lines were resistant. Then, we compared the DEGs between sensitive and resistant group cell lines. We enriched DEGs in GO and KEGG and performed GSEA in each group. Genes in two groups did not show obvious different expressions in EGFR pathways, while Hoshida subclass of HCC seemed to associate with the efficacy of nimotuzumab in that S2 and S3 showed better therapeutic effect than S1. Therefore, we analyzed genes in human tumor samples which were from TCGA-LIHC and GSE102079. We found that COL1A1, COL1A2, COL3A1, and MMP9 were the focus DEGs of S1 and S2 & S3 related to EGFR.
Conclusion: The efficacy of nimotuzumab in HCC did not show direct relevance with EGFR protein expression and EGFR-related pathway. However, efficacy could associate with Hoshida subclass of HCC. Three ECM genes (COL1A1, COL1A2, COL3A1) and MMP9 were paid attention, as they might play important roles in the curative effect of nimotuzumab in HCC.
Keywords: bioinformatic analysis, hepatocellular carcinoma, cell line, nimotuzumab, Hoshida subclass, TCGA, GEO