Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing
Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, emphasizing the need for novel therapeutic strategies. Decorin (DCN), a chondroitin sulfate proteoglycan (CSPG), has been proposed as a tumor suppressor, yet its precise role in HCC and the tumor microenviro...
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2025-05-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03811-0 |
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| author | Chi Hsiao Wen-Chieh Liao Ju-Pi Li Yu-Cheng Chou Yu-Lun Chou Jeng-Rong Lin Chia-Hua Chen Chiung-Hui Liu |
| author_facet | Chi Hsiao Wen-Chieh Liao Ju-Pi Li Yu-Cheng Chou Yu-Lun Chou Jeng-Rong Lin Chia-Hua Chen Chiung-Hui Liu |
| author_sort | Chi Hsiao |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, emphasizing the need for novel therapeutic strategies. Decorin (DCN), a chondroitin sulfate proteoglycan (CSPG), has been proposed as a tumor suppressor, yet its precise role in HCC and the tumor microenvironment (TME) remains underexplored. Through integrated analyses of bulk RNA and single-cell RNA sequencing datasets, we identified a distinct tumor stromal subset highly expressing DCN and associated chondroitin sulfate (CS) synthases. Our findings revealed that DCN expression is significantly downregulated in HCC tissue, but upregulated in peri-tumor stroma, where it correlates with better prognosis and reduced capsular invasion. Western blot analysis demonstrated that CS-DCN, the glycosylated form of DCN, plays a dominant role in this context. Single-cell clustering analysis identified a unique stromal subset in HCC characterized by elevated expression of DCN, CSPGs, and CS synthases, associated with extracellular matrix (ECM) remodeling and protective barrier functions. A six-gene DCN-associated signature derived from this subset, including DCN, BGN, SRPX, CHSY3, CHST3, and CHPF, was validated as a prognostic marker for HCC. Furthermore, functional assays demonstrated that CS-DCN significantly inhibited HCC cell proliferation and invasion. Our study highlights the critical role of DCN in HCC TME and provides insights into its therapeutic potential. Modulating CSPG pathways, particularly on CS-DCN-expressing stromal cells, may offer a promising approach for improving HCC treatment and patient outcomes. |
| format | Article |
| id | doaj-art-ac1f21e4e3b34803885f02a353b56c51 |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-ac1f21e4e3b34803885f02a353b56c512025-08-20T03:22:13ZengBMCCancer Cell International1475-28672025-05-0125111410.1186/s12935-025-03811-0Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencingChi Hsiao0Wen-Chieh Liao1Ju-Pi Li2Yu-Cheng Chou3Yu-Lun Chou4Jeng-Rong Lin5Chia-Hua Chen6Chiung-Hui Liu7Doctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing UniversityDoctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Pathology, School of Medicine, Chung Shan Medical UniversityDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing UniversityDoctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing UniversityDoctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Anatomy, School of Medicine, Chang Gung UniversityDoctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing UniversityAbstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, emphasizing the need for novel therapeutic strategies. Decorin (DCN), a chondroitin sulfate proteoglycan (CSPG), has been proposed as a tumor suppressor, yet its precise role in HCC and the tumor microenvironment (TME) remains underexplored. Through integrated analyses of bulk RNA and single-cell RNA sequencing datasets, we identified a distinct tumor stromal subset highly expressing DCN and associated chondroitin sulfate (CS) synthases. Our findings revealed that DCN expression is significantly downregulated in HCC tissue, but upregulated in peri-tumor stroma, where it correlates with better prognosis and reduced capsular invasion. Western blot analysis demonstrated that CS-DCN, the glycosylated form of DCN, plays a dominant role in this context. Single-cell clustering analysis identified a unique stromal subset in HCC characterized by elevated expression of DCN, CSPGs, and CS synthases, associated with extracellular matrix (ECM) remodeling and protective barrier functions. A six-gene DCN-associated signature derived from this subset, including DCN, BGN, SRPX, CHSY3, CHST3, and CHPF, was validated as a prognostic marker for HCC. Furthermore, functional assays demonstrated that CS-DCN significantly inhibited HCC cell proliferation and invasion. Our study highlights the critical role of DCN in HCC TME and provides insights into its therapeutic potential. Modulating CSPG pathways, particularly on CS-DCN-expressing stromal cells, may offer a promising approach for improving HCC treatment and patient outcomes.https://doi.org/10.1186/s12935-025-03811-0Hepatocellular carcinomaTumor microenvironmentChondroitin polymerizing factorChondroitin sulfateDecorin |
| spellingShingle | Chi Hsiao Wen-Chieh Liao Ju-Pi Li Yu-Cheng Chou Yu-Lun Chou Jeng-Rong Lin Chia-Hua Chen Chiung-Hui Liu Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing Cancer Cell International Hepatocellular carcinoma Tumor microenvironment Chondroitin polymerizing factor Chondroitin sulfate Decorin |
| title | Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing |
| title_full | Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing |
| title_fullStr | Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing |
| title_full_unstemmed | Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing |
| title_short | Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing |
| title_sort | revealing a novel decorin expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single cell rna sequencing |
| topic | Hepatocellular carcinoma Tumor microenvironment Chondroitin polymerizing factor Chondroitin sulfate Decorin |
| url | https://doi.org/10.1186/s12935-025-03811-0 |
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