{"title":"DNAJC24抑制乳腺癌恶性肿瘤并作为预后生物标志物。","authors":"Wenjing Meng, Wei Liu, Yulong Yang, Xiaorui Wang, Linlin Zhan, Yi Luo, Liwei Chen, Yu Wang, Guangtao Li, Yehui Shi, Yuchao He, Zhongsheng Tong, Hua Guo","doi":"10.1186/s12935-025-03918-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Based on the current markers, numerous targeted therapies have been put forward for clinical application; however, treatment resistance and recurrence still remain the main causes of breast cancer-related mortality. In addition, breast cancer exhibits significant heterogeneity, and patients with apparently similar tumor subtypes exhibit variable responses to identical drug treatments. Therefore, accurate prediction of breast cancer progression and personalized treatment plans will maximize patient benefit by avoiding overtreatment and undertreatment.</p><p><strong>Methods: </strong>In this study, our emphasis was placed on exploring the function of DnaJ heat shock protein family member C24 (DNAJC24, also known as DPH4) in breast cancer through bioinformatic analysis by using public databases and clinicopathological samples. We performed in vitro functional assays to explore the biological roles of DNAJC24.</p><p><strong>Results: </strong>Bioinformatics analysis of TCGA data demonstrated significantly lower DNAJC24 expression in breast cancer tissues compared to adjacent paracancer tissues (p < 0.001). Immunohistochemistry showed low DNAJC24 expression in 72.4% (210/290) of breast cancer tissues versus 50.8% (134/264) of adjacent paracancer tissues. DNAJC24 expression decreased progressively with advanced clinical stages (p < 0.05), was lowest in HER2-enriched subtype, and highest in Luminal-A subtype. Overexpression of DNAJC24 in breast cancer cells significantly reduced colony formation (p < 0.05), proliferation rates, chemotaxis (p < 0.05), invasion (p < 0.05), and migration abilities (p < 0.05) compared to controls. Conversely, DNAJC24 knockdown in cancer cells produced opposite effects, significantly enhancing chemotaxis, invasion, and migration (all p < 0.05).</p><p><strong>Conclusions: </strong>Lower DNAJC24 expression is strongly associated with breast cancer malignancy, advanced clinical stages, aggressive molecular subtypes, and poorer prognosis. Functionally, DNAJC24 inhibits proliferation, invasion, and migration of breast cancer cells, underscoring its potential as a prognostic biomarker in breast cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"279"},"PeriodicalIF":6.0000,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291279/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNAJC24 suppresses breast cancer malignancy and serves as a prognostic biomarker.\",\"authors\":\"Wenjing Meng, Wei Liu, Yulong Yang, Xiaorui Wang, Linlin Zhan, Yi Luo, Liwei Chen, Yu Wang, Guangtao Li, Yehui Shi, Yuchao He, Zhongsheng Tong, Hua Guo\",\"doi\":\"10.1186/s12935-025-03918-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Based on the current markers, numerous targeted therapies have been put forward for clinical application; however, treatment resistance and recurrence still remain the main causes of breast cancer-related mortality. In addition, breast cancer exhibits significant heterogeneity, and patients with apparently similar tumor subtypes exhibit variable responses to identical drug treatments. Therefore, accurate prediction of breast cancer progression and personalized treatment plans will maximize patient benefit by avoiding overtreatment and undertreatment.</p><p><strong>Methods: </strong>In this study, our emphasis was placed on exploring the function of DnaJ heat shock protein family member C24 (DNAJC24, also known as DPH4) in breast cancer through bioinformatic analysis by using public databases and clinicopathological samples. We performed in vitro functional assays to explore the biological roles of DNAJC24.</p><p><strong>Results: </strong>Bioinformatics analysis of TCGA data demonstrated significantly lower DNAJC24 expression in breast cancer tissues compared to adjacent paracancer tissues (p < 0.001). Immunohistochemistry showed low DNAJC24 expression in 72.4% (210/290) of breast cancer tissues versus 50.8% (134/264) of adjacent paracancer tissues. DNAJC24 expression decreased progressively with advanced clinical stages (p < 0.05), was lowest in HER2-enriched subtype, and highest in Luminal-A subtype. Overexpression of DNAJC24 in breast cancer cells significantly reduced colony formation (p < 0.05), proliferation rates, chemotaxis (p < 0.05), invasion (p < 0.05), and migration abilities (p < 0.05) compared to controls. Conversely, DNAJC24 knockdown in cancer cells produced opposite effects, significantly enhancing chemotaxis, invasion, and migration (all p < 0.05).</p><p><strong>Conclusions: </strong>Lower DNAJC24 expression is strongly associated with breast cancer malignancy, advanced clinical stages, aggressive molecular subtypes, and poorer prognosis. Functionally, DNAJC24 inhibits proliferation, invasion, and migration of breast cancer cells, underscoring its potential as a prognostic biomarker in breast cancer.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"279\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-07-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291279/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03918-4\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03918-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
DNAJC24 suppresses breast cancer malignancy and serves as a prognostic biomarker.
Background: Based on the current markers, numerous targeted therapies have been put forward for clinical application; however, treatment resistance and recurrence still remain the main causes of breast cancer-related mortality. In addition, breast cancer exhibits significant heterogeneity, and patients with apparently similar tumor subtypes exhibit variable responses to identical drug treatments. Therefore, accurate prediction of breast cancer progression and personalized treatment plans will maximize patient benefit by avoiding overtreatment and undertreatment.
Methods: In this study, our emphasis was placed on exploring the function of DnaJ heat shock protein family member C24 (DNAJC24, also known as DPH4) in breast cancer through bioinformatic analysis by using public databases and clinicopathological samples. We performed in vitro functional assays to explore the biological roles of DNAJC24.
Results: Bioinformatics analysis of TCGA data demonstrated significantly lower DNAJC24 expression in breast cancer tissues compared to adjacent paracancer tissues (p < 0.001). Immunohistochemistry showed low DNAJC24 expression in 72.4% (210/290) of breast cancer tissues versus 50.8% (134/264) of adjacent paracancer tissues. DNAJC24 expression decreased progressively with advanced clinical stages (p < 0.05), was lowest in HER2-enriched subtype, and highest in Luminal-A subtype. Overexpression of DNAJC24 in breast cancer cells significantly reduced colony formation (p < 0.05), proliferation rates, chemotaxis (p < 0.05), invasion (p < 0.05), and migration abilities (p < 0.05) compared to controls. Conversely, DNAJC24 knockdown in cancer cells produced opposite effects, significantly enhancing chemotaxis, invasion, and migration (all p < 0.05).
Conclusions: Lower DNAJC24 expression is strongly associated with breast cancer malignancy, advanced clinical stages, aggressive molecular subtypes, and poorer prognosis. Functionally, DNAJC24 inhibits proliferation, invasion, and migration of breast cancer cells, underscoring its potential as a prognostic biomarker in breast cancer.
期刊介绍:
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.