Zhao Leyi, Xi Lingze, Liu Yani, Wang Guoliang, Zong Mingtong, Xue Peng, Zhu Shijie
School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Biomedicines. 2025 Feb 21;13(3):539. doi: 10.3390/biomedicines13030539.
Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Tertiary lymphoid structures (TLSs), organized immune cell aggregates in non-lymphoid tissues, are linked to chronic inflammation and tumorigenesis. However, the precise relationship between TLSs and CRC prognosis remains unclear. This study aimed to develop a TLS-associated genetic signature to predict CRC prognosis and support clinical applications. Utilizing the TCGA database, we analyzed TLS-related gene expression in CRC versus normal tissues. Prognostic models were constructed using Cox and Kaplan-Meier analyses. CRC samples were stratified into high and low TLS groups via ssGSEA, with validation in the GSE75500 dataset. We identified clinical characteristics associated with TLS scores, created prognostic nomograms, analyzed the top 50 differential genes, assessed tumor mutations, estimated immune infiltration using CIBERSORT, and examined correlations between TLS scores and immune checkpoints. A 13-gene TLS-associated prognostic model for CRC was developed, emphasizing immune response genes. Survival analysis indicated significantly better outcomes for the TLS-high group. Cox regression identified stage IV and M1 as independent factors influencing TLS scores. Nomogram analysis demonstrated that combining TLS scores with clinical features enhances prognostic accuracy. TLS scores were closely associated with immune checkpoint genes, suggesting potential immunotherapy benefits for TLS-high patients. This study developed and validated a TLS-based prognostic model for CRC, exploring relevant immune cells. The model holds promise for predicting clinical prognosis and treatment responsiveness in CRC patients.
结直肠癌（CRC）是全球第三大常见癌症。三级淋巴结构（TLSs）是在非淋巴组织中组织化的免疫细胞聚集体，与慢性炎症和肿瘤发生有关。然而，TLSs与CRC预后的确切关系仍不清楚。本研究旨在开发一种与TLS相关的基因特征，以预测CRC预后并支持临床应用。利用TCGA数据库，我们分析了CRC与正常组织中与TLS相关的基因表达。使用Cox和Kaplan-Meier分析构建预后模型。通过单样本基因集富集分析（ssGSEA）将CRC样本分为高TLS组和低TLS组，并在GSE75500数据集中进行验证。我们确定了与TLS评分相关的临床特征，创建了预后列线图，分析了前50个差异基因，评估了肿瘤突变，使用CIBERSORT估计了免疫浸润，并检查了TLS评分与免疫检查点之间的相关性。开发了一种用于CRC的13基因TLS相关预后模型，重点关注免疫反应基因。生存分析表明，TLS高分组的预后明显更好。Cox回归确定IV期和M1是影响TLS评分的独立因素。列线图分析表明，将TLS评分与临床特征相结合可提高预后准确性。TLS评分与免疫检查点基因密切相关，这表明TLS高的患者可能从免疫治疗中获益。本研究开发并验证了一种基于TLS的CRC预后模型，并探索了相关免疫细胞。该模型有望预测CRC患者的临床预后和治疗反应性。
