Yang Yunxi, Lu Cheng, Li Linbin, Zheng Chunfang, Wang Yifan, Chen Jiahui, Sun Bingwei
Research Center for Neutrophil Engineering Technology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, Jiangsu Province, China.
J Cancer. 2024 Mar 25;15(9):2866-2879. doi: 10.7150/jca.94560. eCollection 2024.
To investigate the role of neutrophils in colon cancer progression. Genetic data from 1,273 patients with colon cancer were procured from public databases and categorized based on genes linked to neutrophils through an unsupervised clustering approach. Through univariate Cox regression analysis, differentially expressed genes (DEGs) influencing overall survival (OS) were identified, forming the basis for establishing a prognostic risk score (PRS) system specific to colon cancer. Additionally, the correlation between PRS and patient prognosis, immune cell infiltration, and intratumoral gene mutations were analyzed. Validation of PRS as an indicator for "pan-tumor" immunotherapy was conducted using four distinct immunotherapy cohorts. The research identified two distinct subtypes of colon cancer, namely Cluster A and B, with patients in Cluster B demonstrating remarkably superior prognoses over those in Cluster A. A total of 17 genes affecting OS were screened based on 109 DEGs between the two cluster for constructing the PRS system. Notably, individuals classified under the high-PRS group (PRS) exhibited poorer prognoses, significantly linked with immune cell infiltration, an immunosuppressive tumor microenvironment, and increased genomic mutations. Remarkably, analysis of immunotherapy cohorts indicated that patients with PRS exhibited enhanced clinical responses, a higher rate of progression-free events, and improved overall survival post-immunotherapy. The PRS system, developed based on tumor typing utilizing neutrophil-associated genes, exhibited a strong correlation with prognostic elements in colon cancer and emerged as a vital predictor of "pan-tumor" immunotherapy efficacy. PRS serves as a prognostic model for patients with colon cancer and holds the potential to act as a "pan-tumor" universal marker for assessing immunotherapy efficacy across different tumor types. The study findings lay a foundation for novel antitumor strategies centered on neutrophil-focused approaches.
为研究中性粒细胞在结肠癌进展中的作用。从公共数据库获取了1273例结肠癌患者的基因数据，并通过无监督聚类方法根据与中性粒细胞相关的基因进行分类。通过单变量Cox回归分析，确定了影响总生存期（OS）的差异表达基因（DEG），为建立结肠癌特异性预后风险评分（PRS）系统奠定了基础。此外，还分析了PRS与患者预后、免疫细胞浸润和肿瘤内基因突变之间的相关性。使用四个不同的免疫治疗队列对PRS作为“泛肿瘤”免疫治疗指标进行了验证。该研究确定了结肠癌的两种不同亚型，即A组和B组，B组患者的预后明显优于A组。基于两组之间的109个DEG筛选出17个影响OS的基因，用于构建PRS系统。值得注意的是，高PRS组（PRS）的个体预后较差，与免疫细胞浸润、免疫抑制性肿瘤微环境和基因组突变增加显著相关。值得注意的是，免疫治疗队列分析表明，PRS患者的临床反应增强，无进展事件发生率更高，免疫治疗后的总生存期改善。基于利用中性粒细胞相关基因进行肿瘤分型开发的PRS系统，与结肠癌的预后因素密切相关，成为“泛肿瘤”免疫治疗疗效的重要预测指标。PRS可作为结肠癌患者的预后模型，并有可能作为评估不同肿瘤类型免疫治疗疗效的“泛肿瘤”通用标志物。该研究结果为以中性粒细胞为重点的新型抗肿瘤策略奠定了基础。
