By integrating single-cell RNA sequencing and bulk RNA sequencing, plasma cells signature and tertiary lymphoid structures were verified to contribute to outcome in lung adenocarcinoma.

IF 1.7 4区医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2025-01-31 Epub Date: 2024-12-20 DOI:10.21037/tcr-24-1746

Zetian Gong, Xianchuang Xu, Yaolin Cao, Yanlong Feng, Jiatao Liu, Jinpeng Yang, Wenyu Wang, Hui Gong, Jun Li, Liang Chen, Wei Wang

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Abstract

Background: Tertiary lymphoid structures (TLS), consisting of T cell zones, B cell follicles, and germinal centers (GCs), are ectopic lymphoid tissue that form within non-lymphoid tissue. It has recently become a focus of attention. The TLS serve as an effective site for generating an anti-tumor inflammatory response by infiltrating immune cells, especially plasma cells. Thus, we aimed to explore the role of both TLS and plasma cells in influencing the prognosis of lung adenocarcinoma (LUAD).

Methods: Single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database, and bulk RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Seurat R package was used to process scRNA-seq data and identify clusters by the marker genes with Kaplan-Meier (KM) curves plotted to predict the prognosis. Finally, hematoxylin and eosin (H&E) staining and multiplex immunofluorescence analysis were conducted to corroborate our suspicions.

Results: Seven clusters were identified in LUAD based on scRNA-seq data, with the number of B cells differing significantly between early and advanced cohorts. The plasma cells were also increased in advanced lung cancer (LC) and the number of TLS was significantly related to tumor stage. Then, via KM method, we confirmed that both plasma cells and TLS were associated with patient outcomes. Finally, H&E staining and multiplex immunofluorescence analysis verified the correlation between the two.

Conclusions: Plasma cells and TLS can effectively predict the prognosis of LUAD. In the tumor microenvironment (TME) of advanced tumors, plasma cells might be in a state of functional exhaustion. Comprehensive characterization of TLS and corresponding B‑cell pathways may help to activate the function of plasma cells and provide new strategies for cancer treatment.

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通过整合单细胞RNA测序和整体RNA测序，证实了浆细胞特征和三级淋巴样结构对肺腺癌预后的影响。

背景：三级淋巴结构（TLS）由T细胞区、B细胞滤泡和生发中心（GCs）组成，是在非淋巴组织中形成的异位淋巴组织。它最近成为人们关注的焦点。TLS是通过浸润免疫细胞，特别是浆细胞产生抗肿瘤炎症反应的有效位点。因此，我们旨在探讨TLS和浆细胞在影响肺腺癌（LUAD）预后中的作用。方法：从Gene Expression Omnibus （GEO）数据库获取单细胞RNA测序（scRNA-seq）数据，从the Cancer Genome Atlas （TCGA）数据库下载大量RNA-seq数据和临床资料。使用Seurat R软件包处理scRNA-seq数据，通过标记基因识别聚类，绘制Kaplan-Meier （KM）曲线预测预后。最后，苏木精和伊红（H&E）染色和多重免疫荧光分析证实了我们的怀疑。结果：基于scRNA-seq数据，在LUAD中鉴定出7个簇，早期和晚期队列中B细胞数量差异显著。晚期肺癌（LC）中浆细胞增多，且TLS数量与肿瘤分期显著相关。然后，通过KM方法，我们证实浆细胞和TLS都与患者预后相关。最后，H&E染色和多重免疫荧光分析证实了两者的相关性。结论：浆细胞和TLS可有效预测LUAD的预后。在晚期肿瘤的肿瘤微环境（tumor microenvironment， TME）中，浆细胞可能处于功能衰竭状态。全面表征TLS及其对应的B细胞通路可能有助于激活浆细胞的功能，并为癌症治疗提供新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.