Jiang Wenying, Wang Maonan, Chen Qingning, Yu Xiaoqian, Liu Guoqian, He Xiaoyun, Mei Cheng, Ou Chunlin
Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, 410000, Hunan, China.
Sci Rep. 2025 Jul 28;15(1):27507. doi: 10.1038/s41598-025-13361-0.
The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (GSCA), and the cBioportal database, we systematically analyzed the expression pattern, prognostic value, methylation status and immune infiltrating association of PRDX gene family members in breast cancer. Through comprehensive analysis, we found that PRDX4 has good prognostic value and is closely related to immune infiltration, and further exploration of its oncogenic function in breast cancer is warranted. Subsequently, we performed a series of cellular assays to explore the potential role of PRDX4 in the progression of breast cancer. We demonstrated that PRDX4 promoted the proliferation, invasion, metastasis, and inhibited the apoptosis of breast cancer cells. In addition, PRDX4 expression was associated with the half maximal inhibitory concentration (IC) of neratinib which primarily targets human epidermal growth factor receptor 2 (HER2) and showed good binding in molecular docking. Our subsequent experiments showed that the PRDX4-HER2 axis may serve as a potential combined target for neratinib therapy. Our findings suggest that PRDX4 may be a potential diagnostic and prognostic marker for breast cancer, and targeting PRDX4 could represent a novel strategy to improve the efficacy of targeted therapy for patients with HER2-positive breast cancer.
乳腺癌的发病率每年持续上升，在预防和治疗方面给世界各国带来了重大挑战。因此，迫切需要确定乳腺癌的新治疗靶点。过氧化物酶（PRDX）家族被认为是各种肿瘤的良好诊断标志物。然而，PRDX家族成员在乳腺癌中的表达及预后意义仍不清楚，需要进行系统研究。通过使用UALCAN、TIMER2.0、人类蛋白质图谱计划（HPA）、基因集癌症分析（GSCA）和cBioportal数据库等生物信息学工具，我们系统地分析了PRDX基因家族成员在乳腺癌中的表达模式、预后价值、甲基化状态和免疫浸润相关性。通过综合分析，我们发现PRDX4具有良好的预后价值，且与免疫浸润密切相关，有必要进一步探索其在乳腺癌中的致癌功能。随后，我们进行了一系列细胞实验，以探讨PRDX4在乳腺癌进展中的潜在作用。我们证明PRDX4促进了乳腺癌细胞的增殖、侵袭、转移，并抑制了其凋亡。此外，PRDX4的表达与主要靶向人表皮生长因子受体2（HER2）的奈拉替尼的半数最大抑制浓度（IC）相关，并且在分子对接中显示出良好的结合。我们随后的实验表明，PRDX4-HER2轴可能作为奈拉替尼治疗的潜在联合靶点。我们的研究结果表明，PRDX4可能是乳腺癌的潜在诊断和预后标志物，靶向PRDX4可能代表一种提高HER2阳性乳腺癌患者靶向治疗疗效的新策略。
