Ren Pengtao, Zhang Yuan
Department of Colorectal Anal Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Electrocardiogram Room, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Front Oncol. 2022 Sep 23;12:1010023. doi: 10.3389/fonc.2022.1010023. eCollection 2022.
In 2011, J. Hoffman, and B. Beutler won the Nobel Prize of medicine for the fact that they discovered the pattern recognition receptors (PRRs) and meanwhile described their effect on cell activation from the innate and adaptive immune systems. There are more and more evidences that have proved the obvious effect of PRRs on tumorigenesis progression. Nevertheless, the overall impact of PRR genes on prognosis, tumor microenvironmental characteristics and treatment response in patients with colon adenocarcinoma (COAD) remains unclear. In this research, we systematically assessed 20 PRR genes and comprehensively identified the prognostic value and enrichment degree of PRRs. The unsupervised clustering approach was employed for dividing COAD into 4 PRR subtypes, namely cluster A, cluster B, cluster C and cluster D, which were significantly different in terms of the clinical features, the immune infiltrations, and the functions. Among them, cluster B has better immune activities and functions. Cox and LASSO regression analysis was further applied to identify a prognostic five-PRR-based risk signature. Such signature can well predict patients' overall survival (OS), together with a good robustness. Confounding parameters were controlled, with results indicating the ability of risk score to independently predict COAD patients' OS. Besides, a nomogram with a strong reliability was created for enhancing the viability exhibited by the risk score in clinical practice. Also, patients who were classified based on the risk score owned distinguishable immune status and tumor mutation status, response to immunotherapy, as well as sensitivity to chemotherapy. A low risk score, featuring increased tumor stemness index (TSI), human leukocyte antigen (HLA), immune checkpoints, and immune activation, demonstrated a superior immunotherapeutic response. According to the study results, the prognostic PRR-based risk signature could serve as a robust biomarker for predicting the clinical outcomes as well as evaluating therapeutic response for COAD patients.
2011年，J. 霍夫曼和B. 博伊特勒因发现模式识别受体（PRRs）并同时描述了它们对先天性和适应性免疫系统中细胞激活的作用而获得诺贝尔医学奖。越来越多的证据证明PRRs对肿瘤发生发展具有显著影响。然而，PRR基因对结肠腺癌（COAD）患者预后、肿瘤微环境特征及治疗反应的总体影响仍不清楚。在本研究中，我们系统评估了20个PRR基因，并全面鉴定了PRRs的预后价值和富集程度。采用无监督聚类方法将COAD分为4种PRR亚型，即A簇、B簇、C簇和D簇，它们在临床特征、免疫浸润和功能方面存在显著差异。其中，B簇具有较好的免疫活性和功能。进一步应用Cox和LASSO回归分析确定了一个基于5个PRR的预后风险特征。该特征能够很好地预测患者的总生存期（OS），且具有良好的稳健性。控制了混杂参数，结果表明风险评分能够独立预测COAD患者的OS。此外，还创建了一个可靠性很强的列线图，以增强风险评分在临床实践中的实用性。而且，根据风险评分分类的患者具有可区分的免疫状态、肿瘤突变状态、对免疫治疗的反应以及对化疗的敏感性。低风险评分具有较高的肿瘤干性指数（TSI）、人类白细胞抗原（HLA）、免疫检查点和免疫激活，显示出更好的免疫治疗反应。根据研究结果，基于PRR的预后风险特征可作为预测COAD患者临床结局及评估治疗反应的有力生物标志物。
