Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma
BackgroundHyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsThe “limma” and “GSVA” packages in R were used to perform differe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1363834/full |
| _version_ | 1797226550843670528 |
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| author | Zhixiong Su Yufang He Lijie You Guifeng Zhang Jingbo Chen Zhenhua Liu |
| author_facet | Zhixiong Su Yufang He Lijie You Guifeng Zhang Jingbo Chen Zhenhua Liu |
| author_sort | Zhixiong Su |
| collection | DOAJ |
| description | BackgroundHyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsThe “limma” and “GSVA” packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and “CellChat” was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the “pRRophetic” package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour.ResultsMultiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. 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 the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy.ConclusionThe results of the present study show that 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. |
| first_indexed | 2024-04-24T14:26:42Z |
| format | Article |
| id | doaj.art-54d5b9f63d0c4e6ba53d70a6b396a4e5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T14:26:42Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-54d5b9f63d0c4e6ba53d70a6b396a4e52024-04-03T04:40:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13638341363834Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinomaZhixiong SuYufang HeLijie YouGuifeng ZhangJingbo ChenZhenhua LiuBackgroundHyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsThe “limma” and “GSVA” packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and “CellChat” was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the “pRRophetic” package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour.ResultsMultiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. 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 the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy.ConclusionThe results of the present study show that 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1363834/fullHMMRHCCsingle cell RNA sequenceRPAtreatmentbulk RNA sequence |
| spellingShingle | Zhixiong Su Yufang He Lijie You Guifeng Zhang Jingbo Chen Zhenhua Liu Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma Frontiers in Immunology HMMR HCC single cell RNA sequence RPA treatment bulk RNA sequence |
| title | Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma |
| title_full | Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma |
| title_fullStr | Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma |
| title_full_unstemmed | Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma |
| title_short | Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma |
| title_sort | coupled scrna seq and bulk seq reveal the role of hmmr in hepatocellular carcinoma |
| topic | HMMR HCC single cell RNA sequence RPA treatment bulk RNA sequence |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1363834/full |
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