Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer
Abstract Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide, with immune cells, particularly dendritic cells (DCs), playing an essential part in the advancement of tumors and immunotherapy response. However, the prognostic significance of genes associated with dendr...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-01792-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850269299577454592 |
|---|---|
| author | Chaobo Chen Zhengqiu Wang Bo Xi Zipeng Xu Chunlong Zhao Weidong Hu Chen Ge Genxi Tong Fengjun Cai Mingli Zhou Yihang Yuan |
| author_facet | Chaobo Chen Zhengqiu Wang Bo Xi Zipeng Xu Chunlong Zhao Weidong Hu Chen Ge Genxi Tong Fengjun Cai Mingli Zhou Yihang Yuan |
| author_sort | Chaobo Chen |
| collection | DOAJ |
| description | Abstract Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide, with immune cells, particularly dendritic cells (DCs), playing an essential part in the advancement of tumors and immunotherapy response. However, the prognostic significance of genes associated with dendritic cells (DCRGs) in COAD remains underexplored. This study aims to identify DCRGs, construct a risk scoring system, and evaluate its prognostic and therapeutic implications. Data from single-cell RNA sequencing (scRNA-seq) of COAD tissues were examined for the detection of DCRGs. Transcriptomic and clinical data from TCGA and GEO were used to construct a DC Related Index (DCRI) via WGCNA, differential expression, univariate Cox regression, and LASSO-Cox analysis. The DCRI was validated in internal and external cohorts. Immune infiltration, MSI status, immune checkpoint expression, and drug sensitivity were analyzed to assess clinical relevance. Functional experiments were performed to investigate the role of PPP2CB in COAD progression. A five-gene signature (CTSD, DAPK1, TIMP1, TBXAS1, PPP2CB) was identified and used to construct a DCRI. The DCRI effectively stratified patients into high- and low-DCRI groups, with significant survival differences. High-DCRI patients exhibited distinct immune infiltration patterns, higher MSI scores, and increased sensitivity to immunotherapy. Functional experiments revealed PPP2CB as a protective factor, with its downregulation inhibits COAD cell proliferation, migration, and invasion. We developed a novel DCRI that accurately predicts COAD prognosis and immunotherapy response. PPP2CB was identified as a potential therapeutic target, offering new insights for personalized COAD treatment strategies. |
| format | Article |
| id | doaj-art-3ea9f5e008384b2b8692695ce4f85a48 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3ea9f5e008384b2b8692695ce4f85a482025-08-20T01:53:11ZengNature PortfolioScientific Reports2045-23222025-05-0115111610.1038/s41598-025-01792-8Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancerChaobo Chen0Zhengqiu Wang1Bo Xi2Zipeng Xu3Chunlong Zhao4Weidong Hu5Chen Ge6Genxi Tong7Fengjun Cai8Mingli Zhou9Yihang Yuan10Department of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of Gastroenterology, Xishan People’s Hospital of Wuxi CityDepartment of Pharmacology, Zunyi Medical UniversityDepartment of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of Gastroenterology, Xishan People’s Hospital of Wuxi CityDepartment of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of General Surgery, Xishan People’s Hospital of Wuxi CityDepartment of General Surgery, Affiliated Wuxi Fifth Hospital of Jiangnan UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing UniversityAbstract Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide, with immune cells, particularly dendritic cells (DCs), playing an essential part in the advancement of tumors and immunotherapy response. However, the prognostic significance of genes associated with dendritic cells (DCRGs) in COAD remains underexplored. This study aims to identify DCRGs, construct a risk scoring system, and evaluate its prognostic and therapeutic implications. Data from single-cell RNA sequencing (scRNA-seq) of COAD tissues were examined for the detection of DCRGs. Transcriptomic and clinical data from TCGA and GEO were used to construct a DC Related Index (DCRI) via WGCNA, differential expression, univariate Cox regression, and LASSO-Cox analysis. The DCRI was validated in internal and external cohorts. Immune infiltration, MSI status, immune checkpoint expression, and drug sensitivity were analyzed to assess clinical relevance. Functional experiments were performed to investigate the role of PPP2CB in COAD progression. A five-gene signature (CTSD, DAPK1, TIMP1, TBXAS1, PPP2CB) was identified and used to construct a DCRI. The DCRI effectively stratified patients into high- and low-DCRI groups, with significant survival differences. High-DCRI patients exhibited distinct immune infiltration patterns, higher MSI scores, and increased sensitivity to immunotherapy. Functional experiments revealed PPP2CB as a protective factor, with its downregulation inhibits COAD cell proliferation, migration, and invasion. We developed a novel DCRI that accurately predicts COAD prognosis and immunotherapy response. PPP2CB was identified as a potential therapeutic target, offering new insights for personalized COAD treatment strategies.https://doi.org/10.1038/s41598-025-01792-8Colon adenocarcinomaDendritic cellsDCRIImmunotherapyPPP2CBPrognosis |
| spellingShingle | Chaobo Chen Zhengqiu Wang Bo Xi Zipeng Xu Chunlong Zhao Weidong Hu Chen Ge Genxi Tong Fengjun Cai Mingli Zhou Yihang Yuan Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer Scientific Reports Colon adenocarcinoma Dendritic cells DCRI Immunotherapy PPP2CB Prognosis |
| title | Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| title_full | Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| title_fullStr | Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| title_full_unstemmed | Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| title_short | Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| title_sort | focusing on dc cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer |
| topic | Colon adenocarcinoma Dendritic cells DCRI Immunotherapy PPP2CB Prognosis |
| url | https://doi.org/10.1038/s41598-025-01792-8 |
| work_keys_str_mv | AT chaobochen focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT zhengqiuwang focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT boxi focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT zipengxu focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT chunlongzhao focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT weidonghu focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT chenge focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT genxitong focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT fengjuncai focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT minglizhou focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer AT yihangyuan focusingondccellstooptimizethepredictionofprognosisandinnovativetreatmentstrategiesforcoloncancer |