Cell diversity and immune infiltration in the parathyroid tumour microenvironment

in Endocrine-Related Cancer
Authors:
Xiang ZhangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Ya HuDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Ming CuiDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Mengyi WangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Xiaobin LiDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Yalu ZhangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Sen YangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Surong HuaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Meiping ShenDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Quan LiaoDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Correspondence should be addressed to Q Liao or M Shen: liaoq@pumch.cn or shenmeiping@jsph.org.cn

*(X Zhang and Y Hu contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-22-0325
Volume/Issue:
Volume 30: Issue 3
Article Type:
Research Article
Article ID:
e220325
Online Publication Date:
16 Feb 2023
Copyright:
© the author(s) 2023
Restricted access

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Tumour microenvironment has been recognized as a crucial factor influencing disease progression. However, relevant features and functions are insufficiently understood in parathyroid neoplasia. Single-cell RNA sequencing was performed to profile the transcriptome of 27,251 cells from 4 parathyroid adenoma (PA) tissue samples. External transcriptomic datasets and immunofluorescence staining of a tissue microarray were set for expression validation. Eight major cell types and various subpopulations were finely identified in PA. We found that a subcluster of tumour endocrine cells with low copy number variation probably presented as a resting state. Diverse infiltrating immune cell subtypes were identified, constructing an immunosuppressive microenvironment. Tumour-associated macrophages, which indicated an anti-inflammatory phenotype, were significantly increased in PA. Inflammatory tumour-associated fibroblasts (iTAFs) were newly verified and highlighted on the role of stromal-immune crosstalk. Positive correlation between iTAFs and increased CD163+ macrophages was uncovered. Moreover, CXCL12 receptor signalling is important for tumour angiogenesis and immune infiltration. Our findings provide a comprehensive landscape interpreting tumour cell heterogeneity, cell diversity, and immune regulation in parathyroid neoplasia. The valuable resources may promote the understanding of parathyroid tumour microenvironment.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e220325
Received Date:
05 Dec 2022
Accepted Date:
12 Dec 2022
Print Publication Date:
01 Mar 2023
Online Publication Date:
16 Feb 2023
Keywords:
parathyroid tumour; single-cell RNA sequencing; tumour-associated macrophage; tumour-associated fibroblast; cell diversity

  • Aibar S, Gonzalez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine JC, Geurts P & Aerts J et al.2017 SCENIC: single-cell regulatory network inference and clustering. Nature Methods 14 1083–1086. (https://doi.org/10.1038/nmeth.4463)

    • Search Google Scholar
    • Export Citation

  • Aran D, Hu Z & Butte AJ 2017 xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biology 18 220. (https://doi.org/10.1186/s13059-017-1349-1)

    • Search Google Scholar
    • Export Citation

  • Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, Nainys J, Wu K, Kiseliovas V & Setty M et al.2018 Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174 1293–1308.e36. (https://doi.org/10.1016/j.cell.2018.05.060)

    • Search Google Scholar
    • Export Citation

  • Chavez-Galan L, Olleros ML, Vesin D & Garcia I 2015 Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages. Frontiers in Immunology 6 263. (https://doi.org/10.3389/fimmu.2015.00263)

    • Search Google Scholar
    • Export Citation

  • Chen K, Wang Q, Li M, Guo H, Liu W, Wang F, Tian X & & Yang Y 2021 Single-cell RNA-seq reveals dynamic change in tumor microenvironment during pancreatic ductal adenocarcinoma malignant progression. eBioMedicine 66 103315. (https://doi.org/10.1016/j.ebiom.2021.103315)

    • Search Google Scholar
    • Export Citation

  • Chen S, Zhu G, Yang Y, Wang F, Xiao YT, Zhang N, Bian X, Zhu Y, Yu Y & Liu F et al.2021 Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression. Nature Cell Biology 23 87–98. (https://doi.org/10.1038/s41556-020-00613-6)

    • Search Google Scholar
    • Export Citation

  • Chen Z, Zhou L, Liu L, Hou Y, Xiong M, Yang Y, Hu J & Chen K 2020 Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nature Communications 11 5077. (https://doi.org/10.1038/s41467-020-18916-5)

    • Search Google Scholar
    • Export Citation

  • Cheung LYM & Rizzoti K 2020 2020 cell population characterization and discovery using single-cell technologies in endocrine systems. Journal of Molecular Endocrinology 65 R35–R51. (https://doi.org/10.1530/JME-19-0276)

    • Search Google Scholar
    • Export Citation

  • Chittezhath M, Dhillon MK, Lim JY, Laoui D, Shalova IN, Teo YL, Chen J, Kamaraj R, Raman L & Lum J et al.2014 Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 41 815–829. (https://doi.org/10.1016/j.immuni.2014.09.014)

    • Search Google Scholar
    • Export Citation

  • Corbetta S, Belicchi M, Pisati F, Meregalli M, Eller-Vainicher C, Vicentini L, Beck-Peccoz P, Spada A & Torrente Y 2009 Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands. American Journal of Pathology 175 1200–1207. (https://doi.org/10.2353/ajpath.2009.080979)

    • Search Google Scholar
    • Export Citation

  • DeLellis RA 2011 Parathyroid tumors and related disorders. Modern Pathology 24(Supplement 2) S78–S93. (https://doi.org/10.1038/modpathol.2010.132)

    • Search Google Scholar
    • Export Citation

  • Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET, Burkhart RA, Teinor JA, Belleau P, Biffi G & Lucito MS et al.2019 Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discovery 9 1102–1123. (https://doi.org/10.1158/2159-8290.CD-19-0094)

    • Search Google Scholar
    • Export Citation

  • Erickson LA & Mete O 2018 Immunohistochemistry in diagnostic parathyroid pathology. Endocrine Pathology 29 113–129. (https://doi.org/10.1007/s12022-018-9527-6)

    • Search Google Scholar
    • Export Citation

  • Grabmaier U, Brandl L, Kreiner J, Negele T, Huber BC, Rimmbach C, David R & Brunner S 2014 Increased numbers of bone marrow-derived cells in parathyroid adenoma. European Journal of Clinical Investigation 44 833–839. (https://doi.org/10.1111/eci.12302)

    • Search Google Scholar
    • Export Citation

  • Guarnieri V, Muscarella LA, Verdelli C & Corbetta S 2018 Alterations of DNA methylation in parathyroid tumors. Molecular and Cellular Endocrinology 469 60–69. (https://doi.org/10.1016/j.mce.2017.05.010)

    • Search Google Scholar
    • Export Citation

  • Haghverdi L, Lun ATL, Morgan MD & Marioni JC 2018 Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors. Nature Biotechnology 36 421–427. (https://doi.org/10.1038/nbt.4091)

    • Search Google Scholar
    • Export Citation

  • Haglund F, Hallstrom BM, Nilsson IL, Hoog A, Juhlin CC & Larsson C 2017 Inflammatory infiltrates in parathyroid tumors. European Journal of Endocrinology 177 445–453. (https://doi.org/10.1530/EJE-17-0277)

    • Search Google Scholar
    • Export Citation

  • Haglund F, Juhlin CC, Kiss NB, Larsson C, Nilsson IL & Hoog A 2016 Diffuse parathyroid hormone expression in parathyroid tumors argues against important functional tumor subclones. European Journal of Endocrinology 174 583–590. (https://doi.org/10.1530/EJE-15-1062)

    • Search Google Scholar
    • Export Citation

  • Hu Y, Zhang X, Wang O, Cui M, Li X, Wang M, Hua S & & Liao Q 2021 Integrated whole-exome and transcriptome sequencing of sporadic parathyroid adenoma. Frontiers in Endocrinology 12 631680. (https://doi.org/10.3389/fendo.2021.631680)

    • Search Google Scholar
    • Export Citation

  • Kanehisa M & Goto S 2000 KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Research 28 27–30. (https://doi.org/10.1093/nar/28.1.27)

    • Search Google Scholar
    • Export Citation

  • Kim IS, Gao Y, Welte T, Wang H, Liu J, Janghorban M, Sheng K, Niu Y, Goldstein A & Zhao N et al.2019 Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms. Nature Cell Biology 21 1113–1126. (https://doi.org/10.1038/s41556-019-0373-7)

    • Search Google Scholar
    • Export Citation

  • Koh J, Hogue JA, Wang Y, DiSalvo M, Allbritton NL, Shi Y, Olson JA & Sosa JA 2016 Single-cell functional analysis of parathyroid adenomas reveals distinct classes of calcium sensing behaviour in primary hyperparathyroidism. Journal of Cellular and Molecular Medicine 20 351–359. (https://doi.org/10.1111/jcmm.12732)

    • Search Google Scholar
    • Export Citation

  • Levitin HM, Yuan J & Sims PA 2018 Single-cell transcriptomic analysis of tumor heterogeneity. Trends in Cancer 4 264–268. (https://doi.org/10.1016/j.trecan.2018.02.003)

    • Search Google Scholar
    • Export Citation

  • Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B & Liu XS 2020 TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Research 48 W509–W514. (https://doi.org/10.1093/nar/gkaa407)

    • Search Google Scholar
    • Export Citation

  • Lloyd RV, Osamura RY, Klöppel G & & Rosai J 2017 WHO/IARC Classification of Tumours. In WHO Classification of Tumours of Endocrine Organs, vol 10, 4th ed. Eds RV lloyd, RY osamura, G Klöppel & J Rosai. Lyon, France: IARC.

    • Search Google Scholar
    • Export Citation

  • Miao YR, Zhang Q, Lei Q, Luo M, Xie GY, Wang H & Guo AY 2020 ImmuCellAI: a unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy. Advanced Science 7 1902880. (https://doi.org/10.1002/advs.201902880)

    • Search Google Scholar
    • Export Citation

  • Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M & Laurila E et al.2003 PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genetics 34 267–273. (https://doi.org/10.1038/ng1180)

    • Search Google Scholar
    • Export Citation

  • Nonaka D 2011 Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions. American Journal of Surgical Pathology 35 145–151. (https://doi.org/10.1097/PAS.0b013e31820371e4)

    • Search Google Scholar
    • Export Citation

  • Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, Rodman C, Luo CL, Mroz EA & Emerick KS et al.2017 Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171 1611–1624.e24. (https://doi.org/10.1016/j.cell.2017.10.044)

    • Search Google Scholar
    • Export Citation

  • Qian J, Olbrecht S, Boeckx B, Vos H, Laoui D, Etioglu E, Wauters E, Pomella V, Verbandt S, Busschaert P & Bassez A et al.2020 A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling. Cell Research 30 745–762. (https://doi.org/10.1038/s41422-020-0355-0)

    • Search Google Scholar
    • Export Citation

  • Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR & Hunter T et al.2020 A framework for advancing our understanding of cancer-associated fibroblasts. Nature Reviews. Cancer 20 174–186. (https://doi.org/10.1038/s41568-019-0238-1)

    • Search Google Scholar
    • Export Citation

  • Satija R, Farrell JA, Gennert D, Schier AF & Regev A 2015 Spatial reconstruction of single-cell gene expression data. Nature Biotechnology 33 495–502. (https://doi.org/10.1038/nbt.3192)

    • Search Google Scholar
    • Export Citation

  • Shi Y, Hogue J, Dixit D, Koh J & & Olson JA 2014 Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia. PNAS 111 3092–3097. (https://doi.org/10.1073/pnas.1319742111)

    • Search Google Scholar
    • Export Citation

  • Shum EY, Walczak EM, Chang C & Christina Fan H 2019 Quantitation of mRNA transcripts and proteins using the BD rhapsody single-cell analysis system. Advances in Experimental Medicine and Biology 1129 63–79. (https://doi.org/10.1007/978-981-13-6037-4_5)

    • Search Google Scholar
    • Export Citation

  • Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR & Lander ES et al.2005 Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. PNAS 102 15545–15550. (https://doi.org/10.1073/pnas.0506580102)

    • Search Google Scholar
    • Export Citation

  • Tirosh I, Izar B, Prakadan SM, Wadsworth MH, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C & Murphy G et al.2016 Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352 189–196. (https://doi.org/10.1126/science.aad0501)

    • Search Google Scholar
    • Export Citation

  • Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, Park JE, Stephenson E, Polanski K & Goncalves A et al.2018 Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563 347–353. (https://doi.org/10.1038/s41586-018-0698-6)

    • Search Google Scholar
    • Export Citation

  • Verdelli C, Avagliano L, Creo P, Guarnieri V, Scillitani A, Vicentini L, Steffano GB, Beretta E, Soldati L & Costa E et al.2015 Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia. Endocrine-Related Cancer 22 87–98. (https://doi.org/10.1530/ERC-14-0161)

    • Search Google Scholar
    • Export Citation

  • Verdelli C, Tavanti GS & Corbetta S 2020 Intratumor heterogeneity in human parathyroid tumors. Histology and Histopathology 35 1213–1228. (https://doi.org/10.14670/HH-18-230)

    • Search Google Scholar
    • Export Citation

  • Verdelli C, Vaira V & Corbetta S 2020 Parathyroid tumor microenvironment. Advances in Experimental Medicine and Biology 1226 37–50. (https://doi.org/10.1007/978-3-030-36214-0_3)

    • Search Google Scholar
    • Export Citation

  • Westin G 2016 Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours. Journal of Internal Medicine 280 551–558. (https://doi.org/10.1111/joim.12458)

    • Search Google Scholar
    • Export Citation

  • Yaari G, Bolen CR, Thakar J & Kleinstein SH 2013 Quantitative set analysis for gene expression: a method to quantify gene set differential expression including gene-gene correlations. Nucleic Acids Research 41 e170. (https://doi.org/10.1093/nar/gkt660)

    • Search Google Scholar
    • Export Citation

  • Zhang L, Yu X, Zheng L, Zhang Y, Li Y, Fang Q, Gao R, Kang B, Zhang Q & Huang JY et al.2018 Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature 564 268–272. (https://doi.org/10.1038/s41586-018-0694-x)

    • Search Google Scholar
    • Export Citation

  • Zhang Q, He Y, Luo N, Patel SJ, Han Y, Gao R, Modak M, Carotta S, Haslinger C & Kind D et al.2019 Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell 179 829–845.e20. (https://doi.org/10.1016/j.cell.2019.10.003)

    • Search Google Scholar
    • Export Citation