Coupled scRNA-Seq and Bulk-seq Reveal the Role of HMMR in Hepatocellular Carcinoma

Abstract Background Hyaluronan-Mediated Motility Receptor (HMMR) has been demonstrated to be overexpressed in multiple carcinomas and to influence the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods The “limma” package in R was used to perform differential expression analysis. The “GSVA” package in R was used to assess the activity of signaling pathways, and inferCNV was used to infer copy number variation (CNV) for each hepatocyte. “CellChat” was used to analyze intercellular communication networks. Recursive partitioning analysis (RPA) was to re-stage HCC patients. The “pRRophetic” package was used to evaluate the IC 50 values of some drugs. Additionally, qRT-PCR was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu assay, and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumor. Results HMMR was over expressed in HCC tissue (compared to normal tissue), which was proved by multiple cohort studies and qRT-PCR. In addition, HMMR had excellent diagnostic performance. HMMR knockdown could inhibit the proliferation and migration of HCC cell lines. Moreover, high HMMR expression was associated with “G2M checkpoint” and “E2F targets” in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of tumor immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively correlated with genomic heterogeneity and patients with high HMMR expression may benefit better from immunotherapy. Moreover, HMMR was associated with poor prognosis in HCC patients and the re-staging by RPA had a good prognosis prediction value and could guide chemotherapy and targeted therapy. Conclusion According to the results of the present study, HMMR could play a role in the diagnosis, prognosis and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses, and is a promising molecular marker for HCC.