Meng Wenjing, Liu Wei, Yang Yulong, Wang Xiaorui, Zhan Linlin, Luo Yi, Chen Liwei, Wang Yu, Li Guangtao, Shi Yehui, He Yuchao, Tong Zhongsheng, Guo Hua
Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Department of Breast Oncology, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, China.
Cancer Cell Int. 2025 Jul 25;25(1):279. doi: 10.1186/s12935-025-03918-4.
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.
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.
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).
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.
基于目前的标志物，已经提出了多种靶向治疗方法用于临床应用；然而，治疗耐药性和复发仍然是乳腺癌相关死亡的主要原因。此外，乳腺癌表现出显著的异质性，肿瘤亚型明显相似的患者对相同药物治疗的反应各不相同。因此，准确预测乳腺癌进展和制定个性化治疗方案将通过避免过度治疗和治疗不足，使患者受益最大化。
在本研究中，我们着重通过使用公共数据库和临床病理样本进行生物信息学分析，来探究DnaJ热休克蛋白家族成员C24（DNAJC24，也称为DPH4）在乳腺癌中的功能。我们进行了体外功能试验，以探究DNAJC24的生物学作用。
对TCGA数据的生物信息学分析表明，与相邻癌旁组织相比，乳腺癌组织中DNAJC24表达显著降低（p < 0.001）。免疫组织化学显示，72.4%（210/290）的乳腺癌组织中DNAJC24表达较低，而相邻癌旁组织中这一比例为50.8%（134/264）。DNAJC24表达随临床分期进展而逐渐降低（p < 0.05），在HER2富集亚型中最低，在Luminal-A亚型中最高。与对照组相比，乳腺癌细胞中DNAJC24的过表达显著降低了集落形成（p < 0.05）、增殖率、趋化性（p < 0.05）、侵袭（p < 0.05）和迁移能力（p < 0.05）。相反，癌细胞中DNAJC24的敲低产生了相反的效果，显著增强了趋化性、侵袭和迁移（所有p < 0.05）。
较低的DNAJC24表达与乳腺癌恶性程度、晚期临床分期、侵袭性分子亚型及较差的预后密切相关。在功能上，DNAJC24抑制乳腺癌细胞的增殖、侵袭和迁移，凸显了其作为乳腺癌预后生物标志物的潜力。
