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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 18

Page:

3459-3467

Research Field:

Publishing date:

Info

Title:

Differential module screening and functional analysis of non-small cell lung cancer mesenchymal stem cells

Author(s):

CHEN Jing¹; 2; LI Heng¹; ZHANG Xiaoping²; ZHAO Yufeng²; LIU Xuechun³; LI Wen⁴; LIU Jun¹; WANG Zhong¹; GU Hao²

1.Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700;2.Data Center of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;3.Chinese Medicine History Literature of China Academy of Chinese Medical Sciences,Beijing 100700,China;4.School of Pharmacy,Lanzhou University,Gansu Lanzhou 730000,China.

Keywords:

module pharmacology; mesenchymal stem cells; non-small cell lung cancer; prognostic biomarker; cell-specific expression; drug target

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2024.18.010

Abstract:

Objective:To analyze the differential modules of mesenchymal stem cells (MSCs) in non-small cell lung cancer (NSCLC),in order to explore the role of differential modules in the molecular mechanism of the occurrence and development of NSCLC and potential therapeutic targets.Methods:Based on GEO high-throughput gene expression profiling data,NSCLC-MSCs gene co-expression network was constructed using module pharmacology platform,and different modules were screened by Zsummary and ME values.GO function analysis and KEGG pathway enrichment analysis were performed on the differential modules.The treatment and prognostic value of different functional genes on lung cancer in the differential modules were analyzed through survival analysis and drug target screening and other methods.Results:A total of 46 NSCLC-MSCs co-expression modules were obtained.Modules No.29,33 and 35 were selected as NSCLC-MSCs differentiation modules.Modules 29,33 and 35 had 175,161 and 156 genes respectively.Module 29 was mainly related to cell regulation and adaptive response,module 33 was related to cellular immune regulation,and module 35 was mainly related to cell metabolic regulation.There were 26,25 and 28 genes in modules 29,33 and 35 that were drug targets respectively.Prognostic analysis showed that 129,105 and 113 genes in modules 29,33 and 35 showed significant prognostic significance (P＜0.01).It was found that 79 (16.1%) regulatory genes related to drug targets and 372 (70.5%) prognostic genes were significant (P＜0.01),indicating that gene clusters in the differential modules have important value in disease treatment and prognosis.Conclusion:The modular pharmacology platform of this study can screen and identify NSCLC-MSCs specific related differential modules,providing method for fine screening of drug targets and prognostic markers.

References:

［1］SIEGEL RL,MILLER KD,FUCHS HE,et al.Cancer statistics,2022［J］.CA:A Cancer Journal for Clinicians,2022,72(1):7-33.
［2］WESTOVER D,ZUGAZAGOITIA J,CHO BC,et al.Mechanisms of acquired resistance to first-and second-generation EGFR tyrosine kinase inhibitors［J］.Annals of Oncology,2018,29:i10-i19.
［3］DE RUYSSCHER D,FAIVRE-FINN C,NACKAERTS K,et al.Recommendation for supportive care in patients receiving concurrent chemotherapy and radiotherapy for lung cancer［J］.Annals of Oncology,2020,31(1):41-49.
［4］KANAYA N,KITAMURA Y,LOPEZ VAZQUEZ M,et al.Gene-edited and-engineered stem cell platform drives immunotherapy for brain metastatic melanomas［J］.Science Translational Medicine,2023,15(698):eade8732.
［5］GOLCHIN A,SHAMS F,KARAMI F.Advancing mesenchymal stem cell therapy with CRISPR/Cas9 for clinical trial studies［J］.Cell Biology and Translational Medicine,2020,8:89-100.
［6］DING W,ZHANG K,LI Q,et al.Advances in understanding the roles of mesenchymal stem cells in lung cancer［J］.Cellular Reprogramming,2023,25(1):20-31.
［7］SUNTEC H,KLEIN D.Lung-resident mesenchymal stem cell fates within lung cancer［J］.Cancers,2021,13(18):4637.
［8］KLOPP AH,GUPTA A,SPAETH E,et al.Concise review:dissecting a disrepancy in the literature:do mesenchymal stem cells support or suppress tumor growth［J］.Stem Cells,2011,29:11-19.
［9］HSU HS,LIN JH,HSU TW,et al.Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway［J］.Lung Cancer,2012,75:167-177.
［10］ZHAO H,XING C,ZHANG J,et al.Comparative efficacy of oral insulin sensitizers metformin,thiazolidinediones,inositol,and berberine in improving endocrine and metabolic profiles in women with PCOS:a network meta-analysis［J］.Reproductive Health,2021,18(1):1-12.
［11］顾浩,陈寅萤,王朋倩,等.基于熵值的冠心病基因网络模块划分方法评价与模块功能相似度分析［J］.中国药理学与毒理学杂志,2018,32(05):377-384. GU H,CHEN YY,WANG PQ,et al.Evaluation and functional similarity analysis of coronary heart disease gene network modules based on entropy［J］.Chinese Journal of Pharmacology and Toxicology,2018,32(05):377-384.
［12］李荣,顾浩,王朋倩,等.九味癥消颗粒配伍治疗肝癌的网络模块分布机制分析［J］.中国实验方剂学杂志,2022,28(15):162-172. LI R,GU H,WANG PQ,et al.Analysis of network module distribution mechanism of Jiuweizhixiao granules in the treatment of hepatocellular carcinoma［J］.Chinese Journal of Experimental Formulae,2022,28(15):162-172.
［13］LI B,ZHANG Y,YU Y,et al.Quantitative assessment of gene expression network module-validation methods［J］.Scientific Reports,2015,5(1):15258.
［14］BARRETT T,WILHITE SE,LEDOUX P,et al.NCBI GEO:archive for functional genomics data sets-update［J］.Nucleic Acids Research,2012,41(D1):D991-D995.
［15］GOTTSCHLING S,GRANZOW M,KUNER R,et al.Mesenchymal stem cells in non-small cell lung cancer-different from others? Insights from comparative molecular and functional analyses［J］.Lung Cancer,2013,80(1):19-29.
［16］LI B,LIU J,YU Y,et al.Network-wide screen identifies variation of novel precise on-module targets using conformational modudaoism［J］.CPT:Pharmacometrics & Systems Pharmacology,2018,7(1):16-25.
［17］ZHOU Y,ZHOU B,PACHE L,et al.Metascape provides a biolo-gist-oriented resource for the analysis of systems-level data-sets［J］.Nature Communications,2019,10(1):1523.
［18］CANNON M,STEVENSON J,STAHL K,et al.DGIdb 5.0:rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms［J］.Nucleic Acids Research,2024,52(D1):D1227-D1235.
［19］HOU GX,LIU P,YANG J,et al.Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter［J］.PLoS One,2017,12(3):e0174515.
［20］GYORFFY B.Transcriptome-level discovery of survival-associated biomarkers and therapy targets in non-small-cell lung cancer［J］.British Journal of Pharmacology,2024,181(3):362-374.
［21］赫捷,吴一龙,高树庚,等.原发性肺癌诊疗指南(2022年版)［J］.中国合理用药探索,2022,19(9):1-28. HE J,WU YL,GAO SG,et al.Guidelines for the diagnosis and treatment of primary lung cancer (2022 edition) ［J］.China Exploration of Rational Drug Use,2022,19(9):1-28.
［22］CHEN XM,SPLINTER PL,TIETZ PS,et al.Phosphatidylinositol 3-kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of Cdc42［J］.Journal of Biological Chemistry,2004,279(30):31671-31678.
［23］JAIN AS,PRASAD A,PRADEEP S,et al.Everything old is new again:Drug repurposing approach for non-small cell lung cancer targeting MAPK signaling pathway［J］.Frontiers in Oncology,2021,11:741326.
［24］SHAHID M,GEORGE TB,SALLER J,et al.FGD4 (Frabin) overexpression in pancreatic neuroendocrine neoplasms［J］.Pancreas,2019,48(10):1307-1311.
［25］VAN DER WEYDEN L,SWIATKOWSKA A,IYER V,et al.A genome-wide screen in mice to identify cell-extrinsic regulators of pulmonary metastatic colonisation［J］.G3:Genes,Genomes,Genetics,2020,10(6):1869-1877.
［26］程京,李勐,李航,等.中医智能装备研究进展与思考［J］.广西医科大学学报,2023,40(04):523-532. CHENG J,LI M,LI H,et al.Research progress and thinking of TCM intelligent equipment ［J］.Journal of Guangxi Medical University,2023,40(04):523-532.
［27］KIM D,YOU E,JEONG J,et al.DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening［J］.Scientific Reports,2017,7(1):6847.
［28］OHHARA Y,TOMARU U,KINOSHITA I,et al.Polymorphisms of the PD-L1 gene 3'-untranslated region are associated with the expression of PD-L1 in non-small cell lung cancer［J］.Genes,Chromosomes and Cancer,2024,63(1):e23216.
［29］MOKSUD N,WAGNER M,PAWELCZYK K,et al.Common inherited variants of PDCD1,CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma［J］.Journal of Cancer Research and Clinical Oncology,2023,149(9):6381-6390.
［30］MURUGESAN K,JIN DX,COMMENT LA,et al.Association of CD274 (PD-L1) copy number changes with immune checkpoint inhibitor clinical benefit in non-squamous non-small cell lung cancer［J］.The Oncologist,2022,27(9):732-739.
［31］STUTVOET TS,KOL A,DE VRIES EG,et al.MAPK pathway activity plays a key role in PD-L1 expression of lung adenocarcinoma cells［J］.The Journal of Pathology,2019,249(1):52-64.
［32］SHIOTA M,MIYAKE H,TAKAHASHI M,et al.Effect of genetic polymorphisms on outcomes following nivolumab for advanced renal cell carcinoma in the SNiP-RCC trial［J］.Cancer Immunology,Immunotherapy,2023,72(6):1903-1915.
［33］LIU B,LI H,LIU X,et al.CircZNF208 enhances the sensitivity to X-rays instead of carbon-ions through the miR-7-5p /SNCA signal axis in non-small-cell lung cancer cells［J］.Cellular Signalling,2021,84:110012.
［34］WANG Z,WANG YY.Modular pharmacology:deciphering the interacting structural organization of the targeted networks［J］.Drug Discovery Today,2013,18(11-12):560-566.
［35］彭学芳.发热伴血小板减少综合征患者外周血免疫细胞变化特征研究［D］.北京：军事科学院,2022. PENG XF.Characteristics of peripheral blood immune cells in patients with fever with thrombocytopenia syndrome［D］.Beijing:Academy of Military Sciences,2022.
［36］徐秀秀.HMEC和MCF7细胞系中microRNA可变转录的研究［D］.南京：南京大学,2017. XU XX.Study on variable transcription of microRNA in HMEC and MCF7 cell lines［D］.Nanjing：Nanjing University,2017.
［37］任兴德.基于细胞类型特异性网络的细胞耦合地图构建与应用［D］.北京：北京中医药大学,2022. REN XD.Construction and application of cell coupling map based on cell type specific network［D］.Beijing：Beijing University of Chinese Medicine,2022.
［38］吴伶俐.通过机器学习模型识别和验证心肌梗死的新型联合铁死亡和铁代谢相关的8个标志基因［D］.长春：吉林大学,2023. WU LL.Identification and validation of a novel combination of 8 marker genes associated with iron death and iron metabolism in myocardial infarction through a machine learning model ［D］.Changchun:Jilin University,2023.
［39］何云艳.乳腺癌化疗患者PICC相关性上肢静脉血栓风险评估模型的构建［D］.蚌埠:蚌埠医学院,2019. HE YY.Construction of a risk assessment model for PICC-associated upper limb venous thrombosis in breast cancer patients treated with chemotherapy［D］.Bengbu:Bengbu Medical College,2019.
［40］SCALA M,BRIGATI G,FIORILLO C,et al.Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings［J］.Neurogenetics.2019,20(3):165-172.
［41］LI C,CHEUNG MKH,HAN S,et al.Mesenchymal stem cells and their mitochondrial transfer:a double-edged sword［J］.Bioscience Reports,2019,39(5):BSR20182417.
［42］HUANG Z,XIAO Z,YU L,et al.Tumor-associated macrophages in non-small-cell lung cancer:From treatment resistance mechanisms to therapeutic targets［J］.Critical Reviews in Oncology/Hematology,2024,196(4):104284.
［43］WHITEHURST AW,BODEMANN BO,CARDENAS J,et al.Synthetic lethal screen identification of chemosensitizer loci in cancer cells［J］.Nature,2007,446:815-819.

Memo

Memo:

National Natural Science Foundation of China(No.81603401);国家自然科学基金青年科学基金项目(编号：81603401);中国中医科学院科技创新工程项目资助(编号：CI2021A05403);中央级公益性科研院所基本科研业务费专项资金资助项目(编号：ZZ13-YQ-078)

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