Gene expression profiling identified TP53MutPIK3CAWild as a potential biomarker for patients with triple-negative breast cancer treated with immune checkpoint inhibitors
Gene expression profiling identified TP53MutPIK3CAWild as a potential biomarker for patients with triple-negative breast cancer treated with immune checkpoint inhibitors
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DOI：
10.3892/ol.2020.11381
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发表时间：
2020-04-01
期刊：
影响因子：
2.9
通讯作者：
Jia, Qingzhu
中科院分区：
文献类型：
--
作者：
Cheng, Jia'nan;Ding, Xiaofang;Jia, Qingzhu
三阴性乳腺癌 (TNBC) 占所有乳腺癌病例的 15-30%，由于缺乏激素或人表皮生长因子受体 2 受体，临床上难以治疗，而这些受体通常是最成功的治疗方法的目标。免疫检查点抑制剂（ICIs）已为多种类型的实体瘤提供了长期生存益处，但反应率较低。因此，迫切需要开发可行的生物标志物来识别有反应的 TNBC 患者。本研究表明，TNBC 的免疫微环境中免疫调节分子的表达量是所有病理类型中最高的。 TNBC的肿瘤突变负荷（TMB）与细胞溶解活性没有很强的相关性，并且与不同程度的免疫细胞浸润和TMB没有显着相关性。机器学习方法根据免疫相关基因是否高表达，将TNBC患者分为“热”肿瘤和“冷”肿瘤两组，两组之间对免疫治疗的反应不同。此外，具有 TP53(Mut)PIK3CA(Wild) 基因型的患者表现出良好的免疫治疗反应特征，并且可能改善 ICI 的治疗效果。总之，本研究表明，TP53和PIK3CA可能是筛选最能从ICIs中受益的患者的合适生物标志物，这可以指导TNBC患者的精准免疫治疗。
Triple-negative breast cancer (TNBC) accounts for 15-30% of all breast cancer cases and is clinically difficult to treat due to the lack of hormone or human epidermal growth factor receptor 2 receptors, which are usually targeted by the most successful therapeutic approaches. Immune checkpoint inhibitors (ICIs) have offered long-term survival benefits in several types of solid tumors, however with low response rates. Thus, there is an urgent need to develop feasible biomarkers for identifying patients with TNBC, who are responsive. The present study demonstrated that the immune microenvironment of TNBC has the highest expression of immunoregulatory molecules among all pathologic types. The tumor mutation burden (TMB) of TNBC was not strongly correlated with cytolytic activity and showed no significant associations with different degrees of immune cell infiltration and TMB. The machine learning method divided patients with TNBC into two groups characterized by 'hot' and 'cold' tumors, according to whether immune-associated genes were highly expressed, and different responses to immunotherapy were seen between these two groups. Furthermore, patients with a TP53(Mut)PIK3CA(Wild) genotype demonstrated favorable immunotherapy-responsive signatures and may have improved outcomes with ICIs. In conclusion, the present study revealed that TP53 and PIK3CA may be appropriate biomarkers to screen for patients who would benefit most from ICIs, which could guide precise immunotherapy for patients with TNBC.