B-341 Effect of chemokine CXCL13-induced tertiary lymphoid structure formation on pathological features and prognosis of non-small cell lung cancer

IF 6.3 2区医学 Q1 MEDICAL LABORATORY TECHNOLOGY

Clinical chemistry Pub Date : 2025-10-02 DOI:10.1093/clinchem/hvaf086.728

H U A Geng, Mengli Xue, Shixiong Li, Meilin Xu

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Abstract

Background The prognosis of patients with non-small cell lung cancer (NSCLC) is closely related to the tumor microenvironment. Studies have shown that the status of tertiary lymphoid structures (TLS) is an important factor affecting the tumor microenvironment. B cell cluster is the main component of TLS, and the C-X-C motif chemokine ligand 13 (CXCL13) is a selective attractant for B cells. However, the relationship between CXCL13 and the formation of TLS remains to be explored. Methods A hundred NSCLC patients who underwent surgical resection in Tianjin Chest Hospital in 2018 were retrospectively recruited. TLS number and maturity were assessed by HE staining and immunohistochemical staining, respectively. The relationship between TLS in tumor tissue and clinicopathological characteristics and prognosis of NSCLC patients was analyzed. The CXCL13 mRNA and protein expression levels were detected by RT-PCR and immunohistochemical staining, respectively. The correlation between CXCL13 in tumor tissue and TLS in tumor microenvironment was analyzed by Spearman correlation.COX regression analysis and Kaplan-Meier survival curve were used to analyze the prognostic effects of TLS and CXCL13 on patients. Results There was no correlation between TLS number or maturity and gender, age, smoking history, histological type, differentiation, pleural invasion, or TNM stage. TLS number and maturity were positively correlated with CD8+ T cell infiltration in tumor tissue (P < 0.05). Kaplan-Meier survival analysis showed that OS was significantly better in patients with greater TLS count, TLS maturity, and CXCL13 expression than those of relatively low values (P < 0.05). The results of multivariate COX regression analysis showed that TLS maturity (P = 0.002) and TNM stage (P < 0.001) were independent predictors of OS in NSCLC patients. Spearman correlation analysis showed that the number and maturity of TLS were positively correlated with CXCL13 mRNA and protein levels. Conclusion The large number of TLS, high TLS maturity, and high CXCL13 expression are associated with good prognosis of NSCLC patients. TLS maturity can be used as a predictor of patient prognosis. Moreover, CXCL13 mRNA and protein expression levels were significantly correlated with TLS number and maturity. CXCL13 may induce B cells to infiltrate the tumor immune microenvironment to promote the formation of TLS in tumor tissues.

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趋化因子cxcl13诱导的三级淋巴样结构形成对非小细胞肺癌病理特征及预后的影响

背景非小细胞肺癌（NSCLC）患者的预后与肿瘤微环境密切相关。研究表明，三级淋巴结构（TLS）的状态是影响肿瘤微环境的重要因素。B细胞簇是TLS的主要组成部分，C-X-C基序趋化因子配体13 （CXCL13）是B细胞的选择性引诱剂。然而，CXCL13与TLS形成的关系还有待进一步研究。方法回顾性分析2018年在天津市胸科医院行手术切除的非小细胞肺癌患者100例。采用HE染色和免疫组化染色分别评价TLS数量和成熟度。分析肿瘤组织中TLS与非小细胞肺癌患者临床病理特征及预后的关系。RT-PCR和免疫组化染色分别检测CXCL13 mRNA和蛋白的表达水平。采用Spearman相关分析肿瘤组织中CXCL13与肿瘤微环境中TLS的相关性。采用COX回归分析和Kaplan-Meier生存曲线分析TLS和CXCL13对患者预后的影响。结果tls数或成熟度与性别、年龄、吸烟史、组织学类型、分化、胸膜侵及TNM分期无关。TLS数量和成熟度与肿瘤组织中CD8+ T细胞浸润呈正相关（P < 0.05）。Kaplan-Meier生存分析显示，TLS计数、TLS成熟度和CXCL13表达较高的患者的OS明显优于相对较低的患者（P < 0.05）。多因素COX回归分析结果显示，TLS成熟度（P = 0.002）和TNM分期（P < 0.001）是NSCLC患者OS的独立预测因子。Spearman相关分析表明，TLS的数量和成熟度与CXCL13 mRNA和蛋白水平呈正相关。结论TLS数量多、TLS成熟度高、CXCL13高表达与NSCLC患者预后良好有关。TLS成熟度可作为患者预后的预测指标。此外，CXCL13 mRNA和蛋白表达水平与TLS数量和成熟度显著相关。CXCL13可能诱导B细胞浸润肿瘤免疫微环境，促进肿瘤组织中TLS的形成。

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来源期刊

Clinical chemistry 医学-医学实验技术

CiteScore

11.30

自引率

4.30%

发文量

212

审稿时长

1.7 months

期刊介绍： Clinical Chemistry is a peer-reviewed scientific journal that is the premier publication for the science and practice of clinical laboratory medicine. It was established in 1955 and is associated with the Association for Diagnostics & Laboratory Medicine (ADLM). The journal focuses on laboratory diagnosis and management of patients, and has expanded to include other clinical laboratory disciplines such as genomics, hematology, microbiology, and toxicology. It also publishes articles relevant to clinical specialties including cardiology, endocrinology, gastroenterology, genetics, immunology, infectious diseases, maternal-fetal medicine, neurology, nutrition, oncology, and pediatrics. In addition to original research, editorials, and reviews, Clinical Chemistry features recurring sections such as clinical case studies, perspectives, podcasts, and Q&A articles. It has the highest impact factor among journals of clinical chemistry, laboratory medicine, pathology, analytical chemistry, transfusion medicine, and clinical microbiology. The journal is indexed in databases such as MEDLINE and Web of Science.