Sung Ji-Yong, Cheong Jae-Ho
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.
Cancers (Basel). 2022 Jun 29;14(13):3191. doi: 10.3390/cancers14133191.
Predicting responses to immune checkpoint blockade (ICB) lacks official standards despite the discovery of several markers. Expensive drugs and different reactivities for each patient are the main disadvantages of immunotherapy. Gastric cancer is refractory and stem-like in nature and does not respond to immunotherapy. In this study, we aimed to identify a characteristic gene that predicts ICB response in gastric cancer and discover a drug target for non-responders. We built and evaluated a model using four machine learning algorithms for two cohorts of bulk and single-cell RNA seq to predict ICB response in gastric cancer patients. Through the LASSO feature selection, we discovered a marker gene signature that distinguishes responders from non-responders. , a candidate characteristic gene selected by all four machine learning algorithms, had a significantly high prevalence in non-responders ( = 0.0019) and showed a poor prognosis ( = 0.0014) at high expression values. This is the first study to discover a signature gene for predicting ICB response in gastric cancer by molecular subtype and provides broad insights into the treatment of stem-like immuno-oncology through precision medicine.
尽管已经发现了几种标志物,但预测免疫检查点阻断(ICB)反应仍缺乏官方标准。昂贵的药物以及每位患者的不同反应性是免疫疗法的主要缺点。胃癌本质上具有难治性和干细胞样特性,对免疫疗法无反应。在本研究中,我们旨在鉴定一种预测胃癌ICB反应的特征基因,并为无反应者发现一个药物靶点。我们使用四种机器学习算法针对两个批量和单细胞RNA测序队列构建并评估了一个模型,以预测胃癌患者的ICB反应。通过LASSO特征选择,我们发现了一种区分反应者和无反应者的标志物基因特征。 ,这是所有四种机器学习算法选择的候选特征基因,在无反应者中具有显著高的患病率( = 0.0019),并且在高表达值时显示出不良预后( = 0.0014)。这是第一项通过分子亚型发现预测胃癌ICB反应的特征基因的研究,并通过精准医学为干细胞样免疫肿瘤学的治疗提供了广泛的见解。