Evidence map›Paper›PMID 40721811›Full record

ArticleJournal of translational medicine2025

Single-cell RNA sequencing reveals a B cell-related immunosuppressive landscape and a potential suppressor in hepatocellular carcinoma.

Wenhao Hou, Jiaqi Jiang, Liyuan Zhu, Hongwei Xu, Lihui Zhu

Abstract read
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Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Wenhao Hou *Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, China.
Jiaqi Jiang *Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, China.
Liyuan ZhuDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, China.
Hongwei XuDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, China.
Lihui ZhuDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, China. sduzhulihui@126.com.ORCID 0000-0002-2624-6506

Funding

National Natural Science Foundation of China-Shandong Joint Fund 82103075Natural Science Foundation of Shandong Province ZR2021QH185
6 · The paper itself

Abstract

backgroundThe sophisticated tumour microenvironment is responsible for the malignant progression and poor prognosis of hepatocellular carcinoma (HCC). Discovering new therapeutic targets is desired for the preferable treatment of HCC patients.

methodsTo characterize the HCC microenvironment, the single-cell transcriptomes of HCC tissues and corresponding noncancerous tissues were analysed. Differentially expressed genes (DEGs), enriched pathways and subgroups were analysed in B cells. Moreover, heterogeneity between malignant and normal hepatocytes was further investigated, which revealed potential biomarkers for HCC progression. The candidate biomarkers were further explored in datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Serum amyloid A2 (SAA2) was detected and further validated in HCC tissues by immunohistochemistry (IHC) and western blot analysis. The biological roles of SAA2 were further investigated in HCC cells.

resultsThe number of B cells in HCC tissues was significantly lower than that in noncancerous tissues, which may result in an immunosuppressive status of the HCC microenvironment. Differentially expressed genes (DEGs) and functional enrichment analysis revealed that B cells might participate in the immunosuppression of HCC by regulating lipid metabolism. Analysis on B cell subgroups demonstrated Naïve B cells were significantly reduced in HCC tissues compared with noncancerous tissues, which indicated that Naïve B cells might be pivotal in the B cell-related immunosuppressive landscape in HCC. Further analysis of hepatocytes revealed highly expressed genes in normal hepatocytes derived from noncancerous liver tissues, which were validated in datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Interestingly, serum amyloid A2 (SAA2) was highly expressed in normal liver tissues compared with HCC tissues. The results were validated in clinical HCC samples by immunohistochemistry (IHC) and western blot assays. Moreover, investigations in HCC cells revealed that SAA2 acted as a tumour suppressor in HCC progression.

conclusionsTaken together, the present findings elucidated the B cell-related immunosuppressive landscape in HCC and identified SAA2 as a novel suppressor in HCC, providing a better understanding of the HCC landscape and suggesting a promising therapeutic target for HCC patients.

Indexed as

B-LymphocytesCarcinoma, HepatocellularImmune ToleranceImmunosuppression TherapyLiver NeoplasmsSequence Analysis, RNASingle-Cell AnalysisCell Line, TumorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleReproducibility of ResultsSerum Amyloid A ProteinTranscriptomeSerum Amyloid A ProteinB cell-related immunosuppressive landscapeHepatocellular carcinomaSerum amyloid A2Single-cell RNA sequencingSuppressorTumour microenvironment

Identifiers

PMID40721811
PMCPMC12306040

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.