Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy
Abstract Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, particularly due to advanced-stage metastasis. P-cadherin (CDH3), a potential therapeutic target, is highly expressed in CRC tissues and associated with poor prognosis and metastasis. However, the mechan...
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BMC
2025-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13845-2 |
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| author | Chen Fu Jia Fu Chaoyue Liu Zhaojin Yu |
| author_facet | Chen Fu Jia Fu Chaoyue Liu Zhaojin Yu |
| author_sort | Chen Fu |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, particularly due to advanced-stage metastasis. P-cadherin (CDH3), a potential therapeutic target, is highly expressed in CRC tissues and associated with poor prognosis and metastasis. However, the mechanisms underlying its role in CRC progression and its translational potential remain poorly understood. Materials and methods This study integrated multiple public databases (TCGA, HCMDB, UALCAN, HPA, UniProt, cBioPortal, and GEO) to evaluate CDH3 expression, construct a prognostic model, and perform functional and translational analyses. Immunohistochemistry was used to validate CDH3 protein expression in clinical samples. Additional analyses included correlations with clinicopathological parameters, immune infiltration (TIDE, TISIDB), functional enrichment (KEGG, GSEA), drug sensitivity (GSCA), and molecular docking (MOE). Single-cell sequencing (CancerSEA, HPA) was also conducted to explore CDH3’s role at the single-cell level. Results CDH3 expression was significantly elevated in CRC tissues and correlated with poor prognosis, recurrence, and metastasis. CDH3 expression was associated with the infiltration of resting immune cells, particularly dendritic cells, and enrichment analysis revealed its critical role in CRC metastasis through extracellular matrix (ECM) and local adhesion pathways. Notably, afatinib emerged as a promising candidate for targeting CDH3 via “drug repositioning,” a process involving the repurposing of existing drugs for new therapeutic applications. Conclusion This study provides novel insights into CDH3’s role in CRC metastasis and its potential as a therapeutic target. The translational potential of CDH3, including its integration with immunotherapy and drug repositioning strategies, offers a promising avenue for the treatment of metastatic CRC. |
| format | Article |
| id | doaj-art-6f2107240de448599f6e7e8fbaf4f4a8 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-6f2107240de448599f6e7e8fbaf4f4a82025-08-20T03:41:14ZengBMCBMC Cancer1471-24072025-03-0125112310.1186/s12885-025-13845-2Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapyChen Fu0Jia Fu1Chaoyue Liu2Zhaojin Yu3Department of Pharmacology, School of Pharmacy, China Medical UniversityDepartment of Pharmacology, School of Pharmacy, China Medical UniversityDepartment of Pharmacology, School of Pharmacy, China Medical UniversityDepartment of Pharmacology, School of Pharmacy, China Medical UniversityAbstract Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, particularly due to advanced-stage metastasis. P-cadherin (CDH3), a potential therapeutic target, is highly expressed in CRC tissues and associated with poor prognosis and metastasis. However, the mechanisms underlying its role in CRC progression and its translational potential remain poorly understood. Materials and methods This study integrated multiple public databases (TCGA, HCMDB, UALCAN, HPA, UniProt, cBioPortal, and GEO) to evaluate CDH3 expression, construct a prognostic model, and perform functional and translational analyses. Immunohistochemistry was used to validate CDH3 protein expression in clinical samples. Additional analyses included correlations with clinicopathological parameters, immune infiltration (TIDE, TISIDB), functional enrichment (KEGG, GSEA), drug sensitivity (GSCA), and molecular docking (MOE). Single-cell sequencing (CancerSEA, HPA) was also conducted to explore CDH3’s role at the single-cell level. Results CDH3 expression was significantly elevated in CRC tissues and correlated with poor prognosis, recurrence, and metastasis. CDH3 expression was associated with the infiltration of resting immune cells, particularly dendritic cells, and enrichment analysis revealed its critical role in CRC metastasis through extracellular matrix (ECM) and local adhesion pathways. Notably, afatinib emerged as a promising candidate for targeting CDH3 via “drug repositioning,” a process involving the repurposing of existing drugs for new therapeutic applications. Conclusion This study provides novel insights into CDH3’s role in CRC metastasis and its potential as a therapeutic target. The translational potential of CDH3, including its integration with immunotherapy and drug repositioning strategies, offers a promising avenue for the treatment of metastatic CRC.https://doi.org/10.1186/s12885-025-13845-2CDH3Colon cancerImmunePrognosisEMTDrug target |
| spellingShingle | Chen Fu Jia Fu Chaoyue Liu Zhaojin Yu Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy BMC Cancer CDH3 Colon cancer Immune Prognosis EMT Drug target |
| title | Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy |
| title_full | Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy |
| title_fullStr | Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy |
| title_full_unstemmed | Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy |
| title_short | Synergistic potential of CDH3 in targeting CRC metastasis and enhancing immunotherapy |
| title_sort | synergistic potential of cdh3 in targeting crc metastasis and enhancing immunotherapy |
| topic | CDH3 Colon cancer Immune Prognosis EMT Drug target |
| url | https://doi.org/10.1186/s12885-025-13845-2 |
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