PuDong Traditional Chinese Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Pudong New Area, China.
Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PeerJ. 2024 Oct 31;12:e18401. doi: 10.7717/peerj.18401. eCollection 2024.
The role of tertiary lymphoid structures (TLS) in oncology is gaining interest, particularly in colorectal carcinoma, yet a thorough analysis remains elusive. This study pioneered a novel TLS quantification system for prognostic and therapeutic response prediction in colorectal carcinoma, alongside a comprehensive depiction of the TLS landscape. Utilizing single-cell sequencing, we established a TLS score within the Tumor Immune Microenvironment (TIME). Analysis of tertiary lymphoid structure-related genes (TLSRGs) in 1,184 patients with colon adenocarcinoma/rectum adenocarcinoma (COADREAD) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases led to the identification of two distinct molecular subtypes. Differentially expressed genes (DEGs) further segregated these patients into gene subtypes. A TLS score was formulated using gene set variation analysis (GSVA) and its efficacy in predicting immunotherapy outcomes was validated in two independent cohorts. High-scoring patients exhibited a 'hot' immune phenotype, correlating with enhanced immunotherapy efficacy. Key genes in our model, including , , , and , were implicated in COADREAD cell proliferation, invasion, and expression. These insights offer a novel approach to colorectal carcinoma treatment, emphasizing TLS targeting as a potential anti-tumor strategy.
三级淋巴结构（TLS）在肿瘤学中的作用越来越受到关注，特别是在结直肠癌中，但全面分析仍难以实现。本研究首创了一种新的结直肠癌预后和治疗反应预测的 TLS 定量系统，同时全面描绘了 TLS 景观。我们利用单细胞测序在肿瘤免疫微环境（TIME）中建立了 TLS 评分。对来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的 1184 名结肠腺癌/直肠腺癌（COADREAD）患者的三级淋巴结构相关基因（TLSRGs）进行分析，确定了两个不同的分子亚型。差异表达基因（DEGs）进一步将这些患者分为基因亚型。使用基因集变异分析（GSVA）构建了 TLS 评分，并在两个独立的队列中验证了其预测免疫治疗结果的功效。高分患者表现出“热”免疫表型，与增强的免疫治疗效果相关。我们模型中的关键基因，包括 、 、 、和 ，与 COADREAD 细胞增殖、侵袭和 表达有关。这些研究结果为结直肠癌治疗提供了一种新方法，强调了靶向 TLS 作为一种潜在的抗肿瘤策略。
