Koni Malvina, Castellano Isabella, Venturelli Emilio, Sarcinella Alessandro, Lopatina Tatiana, Grange Cristina, Cedrino Massimo, Femminò Saveria, Cossu-Rocca Paolo, Orrù Sandra, D'Ascenzo Fabrizio, Cotellessa Ilaria, Tampieri Cristian, Debernardi Carla, Cugliari Giovanni, Matullo Giuseppe, Camussi Giovanni, De Miglio Maria Rosaria, Brizzi Maria Felice
Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
Anatomic Pathology Unit, Department of Diagnostic Services, "Giovanni Paolo II" Hospital, ASL Gallura, 07026 Olbia, Italy.
Cancers (Basel). 2022 Aug 13;14(16):3918. doi: 10.3390/cancers14163918.
Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients' clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases ( = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01-2.2; = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers ( = 0.017, adj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82-0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.
肿瘤分子注释对于生物标志物发现和个性化治疗方法至关重要，尤其是在缺乏有效治疗方案的三阴性乳腺癌（TNBC）中。在本研究中，白细胞介素-3受体α（IL-3Rα）被作为TNBC的预后生物标志物和治疗靶点进行研究。对421例TNBC患者的IL-3Rα表达以及患者的临床和病理特征进行了回顾性分析。IL-3Rα在69%的人类TNBC样本中表达，其表达与淋巴结转移相关（P = 0.026），且总生存期较差（风险比 = 1.50；95%置信区间 = 1.01 - 2.2；P = 0.04）。对癌症基因组图谱（TCGA）的乳腺浸润性癌数据集进行的生物信息学分析证明，与管腔型乳腺癌相比，IL-3Rα在TNBC中高表达（P = 0.017，校正后P = 0.026）。功能研究表明，IL-3Rα激活诱导上皮-内皮和上皮-间充质转化，促进大血腔和肺转移形成，并增加原发性肿瘤和转移灶中程序性细胞死亡配体-1（PD-L1）的表达。基于TCGA数据，提出IL-3Rα、PD-L1和上皮-间充质转化编码基因可用于区分TNBC的侵袭性（曲线下面积 = 0.86，95%置信区间 = 0.82 - 0.89）。总体而言，本研究确定IL-3Rα是TNBC侵袭性的另一种新型生物标志物，并为进一步研究其作为治疗靶点的相关性提供了理论依据。
