Dataset Information

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

ABSTRACT:

Background

Histone chaperones (HCs) are crucial for governing genome stability and gene expression in multiple cancers. However, the functioning of HCs in the tumor microenvironment (TME) is still not clearly understood.

Methods

Self-tested single-cell RNA-seq data derived from 6 breast cancer (BC) patients with brain and liver metastases were reanalyzed by nonnegative matrix factorization (NMF) algorithm for 36 HCs. TME subclusters were observed with BC and immunotherapy public cohorts to assess their prognosis and immune response. The biological effect of HSPA8, one of the HCs, was verified by transwell assay and wound-healing assays.

Results

Cells including fibroblasts, macrophages, B cells, and T cells, were classified into various subclusters based on marker genes. Additionally, it showed that HCs might be strongly associated with biological and clinical features of BC metastases, along with the pseudotime trajectory of each TME cell type. Besides, the results of bulk-seq analysis revealed that TME cell subclusters mediated by HCs distinguished significant prognostic value for BC patients and were relevant to patients' immunotherapy responses, especially for B cells and macrophages. In particular, CellChat analysis exhibited that HCs-related TME cell subclusters revealed extensive and diverse interactions with malignant cells. Finally, transwell and wound-healing assays exhibited that HSPA8 deficiency inhibited BC cell migration and invasion.

Conclusions

Collectively, our study first dissected HCs-guided intercellular communication of TME that contribute to BC metastases.

SUBMITTER: Xie J

PROVIDER: S-EPMC10702093 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

Xie Jindong J Deng Wei W Deng Xinpei X Liang Jie-Ying JY Tang Yuhui Y Huang Jun J Tang Hailin H Zou Yutian Y Zhou Huamao H Xie Xiaoming X

Cancer cell international 20231206 1

<h4>Background</h4>Histone chaperones (HCs) are crucial for governing genome stability and gene expression in multiple cancers. However, the functioning of HCs in the tumor microenvironment (TME) is still not clearly understood.<h4>Methods</h4>Self-tested single-cell RNA-seq data derived from 6 breast cancer (BC) patients with brain and liver metastases were reanalyzed by nonnegative matrix factorization (NMF) algorithm for 36 HCs. TME subclusters were observed with BC and immunotherapy public c ...[more]

PMID: 38057779

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Project description:BackgroundHistone acetylation modification is one of the most common epigenetic methods used to regulate chromatin structure, DNA repair, and gene expression. Existing research has focused on the importance of histone acetylation in regulating tumorigenicity, tumor progression, and tumor microenvironment (TME) but has not explored the potential roles and interactions of histone acetylation regulators in TME cell infiltration, drug sensitivity, and immunotherapy.MethodsThe mRNA expression and genetic alterations of 36 histone acetylation regulators were analyzed in 1599 hepatocellular carcinoma (HCC) samples. The unsupervised clustering method was used to identify the histone acetylation patterns. Then, based on their differentially expressed genes (DEGs), an HAscore model was constructed to quantify the histone acetylation patterns and related subtypes of individual samples. Lastly, the relationship between HAscore and transcription background, tumor clinical features, characteristics of TME, drug response, and efficacy of immunotherapy were analyzed.ResultsWe identified three histone acetylation patterns characterized by high, medium, and low HAscore. Patients with HCC in the high HAscore group experienced worse overall survival time, and the cancer-related malignant pathways were more active in the high HAscore group, comparing to the low HAscore group. The high HAscore group was characterized by an immunosuppressive subtype because of the high infiltration of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells. Following validation, the HAscore was highly correlated with the sensitivity of anti-tumor drugs; 116 therapeutic agents were found to be associated with it. The HAscore was also correlated with the therapeutic efficacy of the PD-L1 and PD-1 blockade, and the response ratio was significantly higher in the low HAscore group.ConclusionTo the best of our knowledge, our study is the first to provide a comprehensive analysis of 36 histone acetylation regulators in HCC. We found close correlations between histone acetylation patterns and tumor malignant pathways and TME. We also analyzed the therapeutic value of the HAscore in targeted therapy and immunotherapy. This work highlights the interactions and potential clinical utility of histone acetylation regulators in treatment of HCC and improving patient outcomes.

Dataset Information

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

Background

Methods

Results

Conclusions

Publications

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

Similar Datasets

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