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Single-cell transcriptome analysis upon ECM-remodeling meningioma cells

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Abstract

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein–protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

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References

  1. Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2020) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro-Oncology 22(Supplement_1):iv1–iv96

    Article  PubMed  PubMed Central  Google Scholar 

  2. Komori T (2017) The 2016 WHO classification of tumours of the central nervous system: the major points of revision. Neurol Med Chir 57(7):301–311

    Article  Google Scholar 

  3. Olar A, Wani KM, Sulman EP, Mansouri A, Zadeh G, Wilson CD, DeMonte F, Fuller GN, Aldape KD (2015) Mitotic index is an independent predictor of recurrence-free survival in meningioma. Brain Pathol 25(3):266–275

    Article  PubMed  Google Scholar 

  4. Wang Z, Wang W, Xu S, Wang S, Tu Y, Xiong Y, Mei J, Wang C (2016) The role of MAPK signaling pathway in the Her-2-positive meningiomas. Oncol Rep 36(2):685–695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sahm F, Schrimpf D, Olar A, Koelsche C, Reuss D, Bissel J, Kratz A, Capper D, Schefzyk S, Hielscher T (2016) TERT promoter mutations and risk of recurrence in meningioma. J Nat Cancer Inst 108(5):djv377

    Article  PubMed  Google Scholar 

  6. Sievers P, Hielscher T, Schrimpf D, Stichel D, Reuss DE, Berghoff AS, Neidert MC, Wirsching H-G, Mawrin C, Ketter R (2020) CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas. Acta Neuropathol 140:409–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sahm F, Schrimpf D, Stichel D, Jones DT, Hielscher T, Schefzyk S, Okonechnikov K, Koelsche C, Reuss DE, Capper DJTlo (2017) DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. lancet oncol 18(5):682–694

  8. Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K (2022) Lucas C-HG, Casey-Clyde TJ, Vasudevan HN: Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities. Nat Genet 54(5):649–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jovic D, Liang X, Zeng H, Lin L, Xu F, Luo Y (2022) Single-cell RNA sequencing technologies and applications: A brief overview. Clin Transl Med 12(3):e694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang AZ, Bowman-Kirigin JA, Desai R, Kang L-I, Patel PR, Patel B, Khan SM, Bender D, Marlin MC, Liu J (2022) Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response. Genome Med 14(1):1–25

    Article  Google Scholar 

  11. Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO (2016) The extracellular matrix: Tools and insights for the “omics” era. Matrix Biol 49:10–24

    Article  CAS  PubMed  Google Scholar 

  12. Butler A, Hoffman P, Smibert P, Papalexi E, Satija R (2018) Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 36(5):411–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Satija R, Farrell JA, Gennert D, Schier AF, Regev A (2015) Spatial reconstruction of single-cell gene expression data. Nat Biotechnol 33(5):495–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang X, Lan Y, Xu J, Quan F, Zhao E, Deng C, Luo T, Xu L, Liao G, Yan M (2019) Cell Marker: a manually curated resource of cell markers in human and mouse. Nucleic Acids Res 47(D1):D721–D728

    Article  CAS  PubMed  Google Scholar 

  15. Young MD, Wakefield MJ, Smyth GK, Oshlack A (2010) Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol 11(2):1–12

    Article  Google Scholar 

  16. Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  CAS  PubMed  Google Scholar 

  18. Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13

    Article  PubMed  Google Scholar 

  19. Mowery CT, Reyes JM, Cabal-Hierro L, Higby KJ, Karlin KL, Wang JH, Kimmerling RJ, Cejas P, Lim K, Li H (2018) Trisomy of a Down syndrome critical region globally amplifies transcription via HMGN1 overexpression. Cell Rep 25(7):1898–1911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P (2019) STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607–D613

    Article  CAS  PubMed  Google Scholar 

  21. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, Rodman C, Luo CL, Mroz EA, Emerick KS (2017) Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171(7):1611–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tirosh I, Izar B, Prakadan SM, Wadsworth MH, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G (2016) Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352(6282):189–196

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hassan C, Afshinnekoo E, Li S, Wu S, Mason CE (2017) Genetic and epigenetic heterogeneity and the impact on cancer relapse. Exp Hematol 54:26–30

    Article  PubMed  PubMed Central  Google Scholar 

  25. McGranahan N, Swanton C (2017) Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168(4):613–628

    Article  CAS  PubMed  Google Scholar 

  26. Morii E (2017) Heterogeneity of tumor cells in terms of cancer-initiating cells. J Toxicol Pathol 30(1):1–6

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  27. Tsoi J, Robert L, Paraiso K, Galvan C, Sheu KM, Lay J, Wong DJL, Atefi M, Shirazi R, Wang X (2018) Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress. Cancer Cell 33(5):890–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Petti AA, Williams SR, Miller CA, Fiddes IT, Srivatsan SN, Chen DY, Fronick CC, Fulton RS, Church DM, Ley TJ (2019) A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing. Nat Commun 10(1):3660

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  29. Apra C, Peyre M, Kalamarides M (2018) Current treatment options for meningioma. Expert Rev Neurother 18(3):241–249

    Article  CAS  PubMed  Google Scholar 

  30. Achey RL, Gittleman H, Schroer J, Khanna V, Kruchko C, Barnholtz-Sloan JS (2019) Nonmalignant and malignant meningioma incidence and survival in the elderly, 2005–2015, using the Central Brain Tumor Registry of the United States. Neuro Oncol 21(3):380–391

    Article  PubMed  Google Scholar 

  31. Youngblood MW, Miyagishima DF, Jin L, Gupte T, Li C, Duran D, Montejo JD, Zhao A, Sheth A, Tyrtova E (2021) Associations of meningioma molecular subgroup and tumor recurrence. Neuro Oncol 23(5):783–794

    Article  CAS  PubMed  Google Scholar 

  32. Pintea B, Boström A, Katsigiannis S, Gousias K, Pintea R, Baumert B, Boström J (2021) Prognostic Factors for Functional Outcome of Patients with Optic Nerve Sheath Meningiomas Treated with Stereotactic Radiotherapy-Evaluation of Own and Meta-Analysis of Published Data. Cancers 13(3):522

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jawhar NMT (2009) Tissue Microarray: A rapidly evolving diagnostic and research tool. Ann Saudi Med 29(2):123–127

    Article  PubMed  PubMed Central  Google Scholar 

  34. Egeblad M, Rasch MG, Weaver VM (2010) Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol 22(5):697–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190):1396–1401

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vasudevan HN, Choudhury A, Hilz S, Villanueva-Meyer JE, Chen WC (2022) Lucas C-HG, Braunstein SE, Oberheim Bush NA, Butowski N, Pekmezci M: Intratumor and informatic heterogeneity influence meningioma molecular classification. Acta Neuropathol 144(3):579–583

    Article  PubMed  PubMed Central  Google Scholar 

  37. Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z (2020) Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun 11(1):5120

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yurchenco PD (2011) Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb Perspect Biol 3(2):a004911

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141(1):52–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE, Hall DMS (2010) Molecular interactions in cancer cell metastasis. Acta Histochem 112(1):3–25

    Article  CAS  PubMed  Google Scholar 

  41. Bourboulia D (2010) Stetler-Stevenson WG: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 20(3):161–168

  42. Sun Z, Guo SS, Fässler R (2016) Integrin-mediated mechanotransduction. J Cell Biol 215(4):445–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wozniak MA, Modzelewska K, Kwong L, Keely PJ (2004) Focal adhesion regulation of cell behavior. Biochimica et Biophysica Acta (BBA)-Mol Cell Res 1692(2–3):103–119

    Article  CAS  Google Scholar 

  44. Schmidt S, Friedl P (2010) Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms. Cell Tissue Res 339(1):83–92

    Article  CAS  PubMed  Google Scholar 

  45. Alkan C, Coe BP, Eichler EE (2011) Genome structural variation discovery and genotyping. Nat Rev Genet 12(5):363–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. MacDonald JR, Ziman R, Yuen RKC, Feuk L, Scherer SW (2014) The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res 42(D1):D986–D992

    Article  CAS  PubMed  Google Scholar 

  47. Ballouz S, Dobin A, Gillis JA (2019) Is it time to change the reference genome? Genome Biol 20(1):1–9

    Article  Google Scholar 

  48. Pös O, Radvanszky J, Buglyó G, Pös Z, Rusnakova D, Nagy B, Szemes T (2021) DNA copy number variation: Main characteristics, evolutionary significance, and pathological aspects. Biomed J 44(5):548–559

    Article  PubMed  PubMed Central  Google Scholar 

  49. Serin Harmanci A, Harmanci AO, Zhou X (2020) CaSpER identifies and visualizes CNV events by integrative analysis of single-cell or bulk RNA-sequencing data. Nat Commun 11(1):89

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ball MW, Gorin MA, Drake CG, Hammers HJ, Allaf ME (2017) The landscape of whole-genome alterations and pathologic features in genitourinary malignancies: an analysis of the cancer genome atlas. Eur Urol Focus 3(6):584–589

    Article  PubMed  PubMed Central  Google Scholar 

  51. Maynard A, McCoach CE, Rotow JK, Harris L, Haderk F, Kerr DL, Elizabeth AY, Schenk EL, Tan W, Zee A (2020) Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 182(5):1232–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Jeong Y, You D, Kang H-G, Yu J, Kim SW, Nam SJ, Lee JE, Kim S (2018) Berberine suppresses fibronectin expression through inhibition of c-Jun phosphorylation in breast cancer cells. J Breast Cancer 21(1):21–27

    Article  PubMed  PubMed Central  Google Scholar 

  54. Jeon M, Lee J, Nam SJ, Shin I, Lee JE, Kim S (2015) Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells. Exp Cell Res 333(1):116–126

    Article  CAS  PubMed  Google Scholar 

  55. Xiao J, Yang W, Xu B, Zhu H, Zou J, Su C, Rong J, Wang T, Chen Z (2018) Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration. BMC Cancer 18(1):1–9

    Article  Google Scholar 

  56. Barresi V, Simbolo M, Fioravanzo A, Piredda ML, Caffo M, Ghimenton C, Pinna G, Longhi M, Nicolato A, Scarpa AJC (2021) Molecular profiling of 22 primary atypical meningiomas shows the prognostic significance of 18q heterozygous loss and cdkn2a/b homozygous deletion on recurrence-free survival. Cancers 13(4):903

  57. Williams EA, Santagata S, Wakimoto H, Shankar GM, Barker FG, Sharaf R, Reddy A, Spear P, Alexander BM, Ross JS (2020) Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic. Acta Neuropathol Commun 8:1–10

    Article  Google Scholar 

  58. Lindblom A, Ruttledge M, Collins VP, Nordenskjöld M, Dumanski JP (1994) Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression. Int J Cancer 56(3):354–357

    Article  CAS  PubMed  Google Scholar 

  59. Nebenfuehr S, Kollmann K, Sexl V (2020) The role of CDK6 in cancer. Int J Cancer 147(11):2988–2995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Xia Y, Liu Y, Yang C, Simeone DM, Sun T-T, DeGraff DJ, Tang M-s, Zhang Y, Wu X-R (2021) Dominant role of CDKN2B/p15INK4B of 9p21. 3 tumor suppressor hub in inhibition of cell-cycle and glycolysis. Nature Commun 12(1):2047

    Article  ADS  CAS  Google Scholar 

  61. Watson MA, Gutmann DH, Peterson K, Chicoine MR, Kleinschmidt-DeMasters BK, Brown HG, Perry A (2002) Molecular characterization of human meningiomas by gene expression profiling using high-density oligonucleotide microarrays. Am J Pathol 161(2):665–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Giammalva GR, Brunasso L, Paolini F, Costanzo R, Bonosi L, Benigno UE, Ferini G, Sava S, Colarossi C, Umana GE (2022) The Long and Winding Road: An Overview of the Immunological Landscape of Intracranial Meningiomas. Cancers 14(15):3639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G (2021) The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol 23(8):1231–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to express our gratitude to Raleigh et al. for making their data publicly available.

Funding

The study was supported by Fundamental Research Program of Shanxi Province (Grant No. 202203021222364).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

    Wen-Qiang Che, Liu Yang & Hong-Qin Wang

  2. Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China

    Wen-Qiang Che & Xiang-Yu Wang

  3. Department of Pathology, Shanxi Provincial People’s Hospital, Taiyuan, 030012, China

    Yu-Jiao Wang

  4. Department of Clinical Research, the First Affiliated Hospital of Jinan University, Guangzhou, 510632, China

    Jun Lyu

  5. Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China

    Jun Lyu

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Contributions

WQC conducted the study design, data curation, and analysis. WQC, LY, and YJW drafted and reviewed the manuscript. All authors have read and approved the final version.

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Correspondence to Hong-Qin Wang, Xiang-Yu Wang or Jun Lyu.

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The authors declare no competing interests.

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The ScRNA-seq data of human meningioma samples (accession number GSE185655) were available from the GEO database.

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Public and freely available data were used; no ethical approval was needed.

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Che, WQ., Wang, YJ., Yang, L. et al. Single-cell transcriptome analysis upon ECM-remodeling meningioma cells. Neurosurg Rev 47, 118 (2024). https://doi.org/10.1007/s10143-024-02349-5

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