肺鳞状细胞癌中的MSR1：泛癌和单细胞分析以及一项队列研究中的预后和免疫学价值

MSR1 in lung squamous cell carcinoma: Prognostic and immunological values in pan-cancer and single-cell analyses and a cohort study.

作者信息

Bu Yuxiang, Liu Yiqian, Hu Chenyue, Yuan Dongchen, Luo Lianxiang, Li Manshan, Hu Jing, Hang Dong, Xu Zhipeng

机构信息

Department of Pathogen Biology, Key Laboratory for Pathogen Infection and Control of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China; The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Pathogen Biology, Key Laboratory for Pathogen Infection and Control of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Oncology, The first Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

出版信息

Int Immunopharmacol. 2025 Jan 3;145:113811. doi: 10.1016/j.intimp.2024.113811. Epub 2024 Dec 11.

DOI:10.1016/j.intimp.2024.113811

PMID:39667048

Abstract

OBJECTIVE

Lung squamous cell carcinoma (LUSC) constitutes approximately 40% of lung cancer cases and lacks effective treatments, needing new diagnostic and prognostic tools. Macrophage scavenger receptor 1 (MSR1), as a key receptor in macrophages, is essential in tumor immunity. However, its mechanisms in regulating tumor progression and immunity and its prognostic value in LUSC remain unclear.

MATERIALS AND METHODS

MSR1 expression in pan-cancer, particularly LUSC across distinct clinical subgroups, was identified utilizing TIMER, GEPIA, and UALCAN databases. Prognosis analysis of MSR1 in pan-cancer was conducted using SangerBox, GEPIA, PrognoScan and Kaplan-Meier plotter. Using SangerBox and TIMER, association between MSR1 expression and infiltrating immune cells was investigated. MSR1 gene co-expression network and Gene Set Enrichment Analysis (GSEA) in LUSC were constructed using LinkedOmics database. The analysis of single-cell RNA-sequencing (scRNA-seq) was conducted using the GEO database. Association between plasma MSR1 levels and LUSC risk was evaluated in a cohort study with 49,566 UK Biobank participants.

RESULTS

MSR1 was dysregulated in various cancers and lowly expressed in LUSC tissues than in the normal. Higher MSR1 expression was substantially correlated with poor LUSC overall survival. MSR1 positively associated with tumor-associated macrophage (TAM) infiltrations and its markers (CCL2, CD68, IL10). MRS1 closely related to the immune-suppression of macrophages in LUSC. Higher plasma MSR1 levels were positively correlated with increased LUSC risk (HR = 1.33, 95 % CI: 1.07-1.64; P = 0.01).

CONCLUSIONS

MSR1 has significant prognostic and immunological values in pan-cancer and represents a possible biomarker for prognosis and diagnosis in LUSC patients.

摘要

目的

肺鳞状细胞癌（LUSC）约占肺癌病例的40%，且缺乏有效的治疗方法，需要新的诊断和预后工具。巨噬细胞清道夫受体1（MSR1）作为巨噬细胞中的关键受体，在肿瘤免疫中至关重要。然而，其在调节肿瘤进展和免疫中的机制以及在LUSC中的预后价值仍不清楚。

材料与方法

利用TIMER、GEPIA和UALCAN数据库确定MSR1在泛癌中的表达，特别是在不同临床亚组的LUSC中的表达。使用SangerBox、GEPIA、PrognoScan和Kaplan-Meier绘图仪对MSR1在泛癌中的预后进行分析。使用SangerBox和TIMER研究MSR1表达与浸润性免疫细胞之间的关联。利用LinkedOmics数据库构建LUSC中的MSR1基因共表达网络和基因集富集分析（GSEA）。使用GEO数据库进行单细胞RNA测序（scRNA-seq）分析。在一项对49566名英国生物银行参与者的队列研究中评估血浆MSR1水平与LUSC风险之间的关联。

结果

MSR1在多种癌症中表达失调，在LUSC组织中的表达低于正常组织。较高的MSR1表达与LUSC较差的总生存期显著相关。MSR1与肿瘤相关巨噬细胞（TAM）浸润及其标志物（CCL2、CD68、IL10）呈正相关。MRS1与LUSC中巨噬细胞的免疫抑制密切相关。较高的血浆MSR1水平与LUSC风险增加呈正相关（HR = 1.33，95%CI：1.07 - 1.64；P = 0.01）。