Tang Lijuan, Zhang Zhe, Fan Jun, Xu Jing, Xiong Jiashen, Tang Lu, Jiang Yan, Zhang Shu, Zhang Gang, Luo Wentian, Xu Yan
Department of Breast and Thyroid Surgery, Daping Hospital, Army Military Medical University, Chongqing, China.
Front Pharmacol. 2023 Jun 23;14:1195864. doi: 10.3389/fphar.2023.1195864. eCollection 2023.
Immunotherapy is a promising strategy for triple-negative breast cancer (TNBC) patients, however, the overall survival (OS) of 5-years is still not satisfactory. Hence, developing more valuable prognostic signature is urgently needed for clinical practice. This study established and verified an effective risk model based on machine learning methods through a series of publicly available datasets. Furthermore, the correlation between risk signature and chemotherapy drug sensitivity were also performed. The findings showed that comprehensive immune typing is highly effective and accurate in assessing prognosis of TNBC patients. Analysis showed that IL18R1, BTN3A1, CD160, CD226, IL12B, GNLY and PDCD1LG2 are key genes that may affect immune typing of TNBC patients. The risk signature plays a robust ability in prognosis prediction compared with other clinicopathological features in TNBC patients. In addition, the effect of our constructed risk model on immunotherapy response was superior to TIDE results. Finally, high-risk groups were more sensitive to MR-1220, GSK2110183 and temsirolimus, indicating that risk characteristics could predict drug sensitivity in TNBC patients to a certain extent. This study proposes an immunophenotype-based risk assessment model that provides a more accurate prognostic assessment tool for patients with TNBC and also predicts new potential compounds by performing machine learning algorithms.
免疫疗法是三阴性乳腺癌(TNBC)患者的一种有前景的治疗策略,然而,5年总生存期(OS)仍不尽人意。因此,临床实践迫切需要开发更有价值的预后特征。本研究通过一系列公开可用数据集,基于机器学习方法建立并验证了一个有效的风险模型。此外,还进行了风险特征与化疗药物敏感性之间的相关性研究。研究结果表明,综合免疫分型在评估TNBC患者预后方面高效且准确。分析表明,IL18R1、BTN3A1、CD160、CD226、IL12B、GNLY和PDCD1LG2是可能影响TNBC患者免疫分型的关键基因。与TNBC患者的其他临床病理特征相比,风险特征在预后预测方面具有强大的能力。此外,我们构建的风险模型对免疫治疗反应的影响优于TIDE结果。最后,高危组对MR - 1220、GSK2110183和替西罗莫司更敏感,这表明风险特征在一定程度上可以预测TNBC患者的药物敏感性。本研究提出了一种基于免疫表型的风险评估模型,为TNBC患者提供了更准确的预后评估工具,并且通过执行机器学习算法预测了新的潜在化合物。