Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, People's Republic of China.
Sci Rep. 2023 Aug 19;13(1):13542. doi: 10.1038/s41598-023-40042-7.
Tertiary lymphoid structures (TLSs) play a crucial role in determining prognosis and response to immunotherapy in several solid malignancies. Nevertheless, the effect of TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) cohort in patients with breast cancer (BRCA) remains controversial. Based on TCGA-BRCA dataset (n = 866), 9-gene was identified to construct an TLS signature and further analyzed its prognostic value. Then, we explored the relationship of this TLS signature with molecular subtype, immune microenvironment, tumor mutational burden (TMB). High-TLS signature patients had a better overall survival (OS) than low-TLS signature patients, consistent with the results in the METABRIC cohort. Multivariate analysis revealed that TLS signature remained an independent prognostic indicator for OS. In addition, we established a nomogram with the integration of TLS signature and other independent variables to predict individual risk of death. The comprehensive results showed that patients with high TLS signature benefit from immunotherapy; the signature was also correlated with inhibition of cell proliferation pathways, low TP53 mutation rate, high infiltration of B cells, CD8 + T cells, CD4 + T cells, and M1 macrophages. Therefore, TLS signature is a promising biomarker to distinguish the prognosis and immune microenvironment in BRCA.
三级淋巴结构 (TLSs) 在几种实体恶性肿瘤中对预后和免疫治疗反应的判断起着至关重要的作用。然而，基于癌症基因组图谱 (TCGA) 队列的 TLS 相关基因特征在乳腺癌 (BRCA) 患者中的作用仍存在争议。基于 TCGA-BRCA 数据集 (n=866)，确定了 9 个基因来构建 TLS 特征，并进一步分析其预后价值。然后，我们探讨了该 TLS 特征与分子亚型、免疫微环境、肿瘤突变负荷 (TMB) 的关系。高-TLS 特征患者的总生存期 (OS) 优于低-TLS 特征患者，与 METABRIC 队列的结果一致。多变量分析显示，TLS 特征仍然是 OS 的独立预后指标。此外，我们建立了一个包含 TLS 特征和其他独立变量的列线图，以预测个体死亡风险。综合结果表明，高 TLS 特征的患者受益于免疫治疗；该特征与抑制细胞增殖途径、低 TP53 突变率、B 细胞、CD8+T 细胞、CD4+T 细胞和 M1 巨噬细胞浸润有关。因此，TLS 特征是区分 BRCA 患者预后和免疫微环境的有前途的生物标志物。
