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SIRPG promotes lung squamous cell carcinoma pathogenesis via M1 macrophages: a multi-omics study integrating data and Mendelian randomization

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机构： [1]Department of Thoracic Surgery, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China, [2]Department of Respiratory and Critical Care Medicine, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China, [3]Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China, [4]Department of Clinical Laboratory, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China, [5]Department of Oncology, Jiangsu Institute of Hematology, Suzhou, China, [6]Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, [7]Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, [8]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China

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关键词： squamous cell carcinoma of the lung Mendelian randomization RNA-seq immune infiltration SIRPG

摘要：

Squamous cell carcinoma of the lung (LUSC) is a severe and highly lethal malignant tumor of the respiratory system, and its molecular mechanisms at the molecular level remain unc\lear.We acquired RNA-seq data from 8 surgical samples obtained from early-stage LUSC and adjacent non-cancerous tissues from 3 different centers. Utilizing Deseq2, we identified 1088 differentially expressed genes with |LogFC| > 1 and a p-value < 0.05 threshold. Furthermore, through MR analysis of Exposure Data for 26,153 Genes and 63,053 LUSC Patients, incorporating 7,838,805 SNPs as endpoints, we identified 213 genes as potential exposure factors.After intersecting the results, we identified 5 differentially expressed genes, including GYPE, PODXL2, RNF182, SIRPG, and WNT7A. PODXL2 (OR 95% CI, 1.169 (1.040 to 1.313)) was identified as an exposed risk factor, with p-values less than 0.01 under the inverse variance weighted model. GO and KEGG analyses revealed enhanced ubiquitin-protein transferase activity and activation of pathways such as the mTOR signaling pathway and Wnt signaling pathway. Immune infiltration analysis showed downregulation of Plasma cells, T cells regulatory (Tregs), and Dendritic cells activated by the identified gene set, while an enhancement was observed in Macrophages M1. Furthermore, we externally validated the expression levels of these five genes using RNA-seq data from TCGA database and 11 GEO datasets of LUSC, and the results showed SIRPG could induce LUSC.SIRPG emerged as a noteworthy exposure risk factor for LUSC. Immune infiltration analysis highlighted Macrophages M1 and mTOR signaling pathway play an important role in LUSC.Copyright © 2024 Mao, Li, Wang, Yu, Han, Xiang, Zhang, Zeng, Jiang and Ma.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

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Q2 ONCOLOGY

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Q2 ONCOLOGY

影响因子： 3.5 最新[2023版] 4 最新五年平均 3.5 出版当年[2023版] 0 出版当年五年平均 3.5 出版前一年[2023版]

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第一作者机构： [1]Department of Thoracic Surgery, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China,

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通讯作者：

通讯机构： [1]Department of Thoracic Surgery, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China, [2]Department of Respiratory and Critical Care Medicine, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou, China, [3]Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China, [8]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China

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SIRPG promotes lung squamous cell carcinoma pathogenesis via M1 macrophages: a multi-omics study integrating data and Mendelian randomization

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