Gene expression profile in metastatic and non-metastatic parathyroid carcinoma

in Endocrine-Related Cancer
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  • 1 Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
  • 2 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • 3 Endocrine Unit, University Hospital of Pisa, Pisa, Italy
  • 4 Division of Surgical Pathology, University Hospital of Pisa, Pisa, Italy
  • 5 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  • 6 Department of Information Engineering, University of Pisa, Pisa, Italy
  • 7 Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Laboratory of Oncology, San Giovanni Rotondo (FG), Italy
  • 8 Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Unit of Pathology, San Giovanni Rotondo (FG), Italy
  • 9 Fondazione IRCCS G. Pascale, Thyroid and Parathyroid Surgery Unit, Istituto Nazionale Tumori, Naples, Italy
  • 10 Endocrinology Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  • 11 Department of Medicine, Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, Italy
  • 12 Department of Medical Sciences and Public Health, Endocrinology Unit, University of Cagliari, Cagliari, Italy

Correspondence should be addressed to F Cetani: cetani@endoc.med.unipi.it

*(V Condello and F Cetani contributed equally to this work)

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Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs PAs and in metastatic PCs vs non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.

Supplementary Materials

    • Supplemetary Table 1. Significant differentially expressed genes and type of regulation
    • Supplementary Table 2. Canonical pathways and associated molecules

 

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  • Abbona GC, Papotti M, Gasparri G & Bussolati G 1995 Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining. Human Pathology 26 135138. (https://doi.org/10.1016/0046-8177(9590028-4)

    • Search Google Scholar
    • Export Citation
  • Adam MA, Untch BR & Olson JA 2010 Parathyroid carcinoma: current understanding and new insights into gene expression and intraoperative parathyroid hormone kinetics. Oncologist 15 6172. (https://doi.org/10.1634/theoncologist.2009-0185)

    • Search Google Scholar
    • Export Citation
  • Agarwal SK, Schröck E, Kester MB, Burns AL, Heffess CS, Ried T & Marx SJ 1998 Comparative genomic hybridization analysis of human parathyroid tumors. Cancer Genetics and Cytogenetics 106 3036. (https://doi.org/10.1016/s0165-4608(9800049-1)

    • Search Google Scholar
    • Export Citation
  • Amendola PG, Reuten R & Terra Erler JT 2019 Interplay between LOX enzymes and integrins in the tumor microenvironment. Cancers 11 729745. (https://doi.org/10.3390/cancers11050729)

    • Search Google Scholar
    • Export Citation
  • Asare EA, Silva-Figueroa A, Hess KR, Busaidy N, Graham PH, Grubbs EG, Lee JE, Williams MD & Perrier ND 2019 Risk of distant metastasis in parathyroid carcinoma and its effect on survival: a retrospective review from a High-Volume Center. Annals of Surgical Oncology 26 35933599. (https://doi.org/10.1245/s10434-019-07451-3)

    • Search Google Scholar
    • Export Citation
  • Barillari G 2020 The impact of matrix metalloproteinase-9 on the sequential steps of the metastatic process. International Journal of Molecular Sciences 21 4526. (https://doi.org/10.3390/ijms21124526)

    • Search Google Scholar
    • Export Citation
  • Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H & Sleeman JP 2005 CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Research 65 1078310793. (https://doi.org/10.1158/0008-5472.CAN-05-0619)

    • Search Google Scholar
    • Export Citation
  • Bilezikian JP, Bandeira L, Khan A & Cusano NE 2018 Hyperparathyroidism. Lancet 391 168178. (https://doi.org/10.1016/S0140-6736(1731430-7)

  • Botti G, Scognamiglio G, Aquino G, Liguori G & Cantile M 2019 LncRNA HOTAIR in tumor microenvironment: what role? International Journal of Molecular Sciences 20 22792290. (https://doi.org/10.3390/ijms20092279)

    • Search Google Scholar
    • Export Citation
  • Brewer K, Costa-Guda J & Arnold A 2019 Molecular genetic insights into sporadic primary hyperparathyroidism. Endocrine-Related Cancer 26 R53R72. (https://doi.org/10.1530/ERC-18-0304)

    • Search Google Scholar
    • Export Citation
  • Cardoso L, Stevenson M & Thakker RV 2017 Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma. Human Mutation 38 16211648. (https://doi.org/10.1002/humu.23337)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, Ambrogini E, Gazzerro E, Colussi G & Berti P et al. 2004 Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. Journal of Clinical Endocrinology and Metabolism 89 55835591. (https://doi.org/10.1210/jc.2004-0294)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Ambrogini E, Viacava P, Pardi E, Fanelli G, Naccarato AG, Borsari S, Lemmi M, Berti P & Miccoli P et al. 2007 Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? European Journal of Endocrinology 156 547554. (https://doi.org/10.1530/EJE-06-0720)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Banti C, Pardi E, Borsari S, Viacava P, Miccoli P, Torregrossa L, Basolo F, Pelizzo MR & Rugge M et al. 2013 CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer. Endocrine Connections 2 186195. (https://doi.org/10.1530/EC-13-0046)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Pardi E & Marcocci C 2016 Update on parathyroid carcinoma. Journal of Endocrinological Investigation 39 595606. (https://doi.org/10.1007/s40618-016-0447-3)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Saponaro F, Borsari S & Marcocci C 2019a Familial and hereditary forms of primary hyperparathyroidism. Frontiers of Hormone Research 51 4051. (https://doi.org/10.1159/000491037)

    • Search Google Scholar
    • Export Citation
  • Cetani F, Marcocci C, Torregrossa L & Pardi E 2019b Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors. Endocrine-Related Cancer 26 R441R464. (https://doi.org/10.1530/ERC-19-0135)

    • Search Google Scholar
    • Export Citation
  • Chen SZ, Yao HQ, Zhu SZ, Li QY, Guo GH & Yu J 2015 Expression levels of matrix metalloproteinase-9 in human gastric carcinoma. Oncology Letters 9 915919. (https://doi.org/10.3892/ol.2014.2768)

    • Search Google Scholar
    • Export Citation
  • Chiofalo MG, Sparaneo A, Chetta M, Franco R, Baorda F, Cinque L, Granatiero M, D’Agruma L, Pezzullo L & Scillitani A et al. 2014 A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome. Cellular Oncology 37 281288. (https://doi.org/10.1007/s13402-014-0187-3)

    • Search Google Scholar
    • Export Citation
  • Condello V, Torregrossa L, Sartori C, Denaro M, Poma AM, Piaggi P, Valerio L, Materazzi G, Elisei R & Vitti P et al. 2019 mRNA and miRNA expression profiling of follicular variant of papillary thyroid carcinoma with and without distant metastases. Molecular and Cellular Endocrinology 479 93102. (https://doi.org/10.1016/j.mce.2018.09.005)

    • Search Google Scholar
    • Export Citation
  • Costa-Guda J, Imanishi Y, Palanisamy N, Kawamata N, Phillip Koeffler H, Chaganti RSK & Arnold A 2013 Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins. Endocrine 44 489495. (https://doi.org/10.1007/s12020-013-9903-4)

    • Search Google Scholar
    • Export Citation
  • DeLellis R, Larsson C, Arnold A, Lloy R, Bilezikian J, Mete O & Eng C 2017 Tumors of the parathyroid glands. In WHO Classification of Tumors of Endocrine Organs, 4th ed., pp. 145159. Eds Lloyd R, Osamura R, Kloppel G, Rosai JLyon, France: IARC Press.

    • Search Google Scholar
    • Export Citation
  • Du WW, Yang W & Yee AJ 2013 Roles of versican in cancer biology-tumorigenesis, progression and metastasis. Histology and Histopathology 28 7017 13. (https://doi.org/10.14670/HH-28.701)

    • Search Google Scholar
    • Export Citation
  • Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA & Lloyd RV 1999 Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. American Journal of Surgical Pathology 23 288295. (https://doi.org/10.1097/00000478-199903000-00007)

    • Search Google Scholar
    • Export Citation
  • Feng Y, Xiong Y, Qiao T, Li X, Jia L & Han Y 2018 Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Medicine 7 61246136. (https://doi.org/10.1002/cam4.1820)

    • Search Google Scholar
    • Export Citation
  • Fernandez-Ranvier GG, Khanafshar E, Tacha D, Wong M, Kebebew E, Duh QY & Clark OH 2009 Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer 115 334344. (https://doi.org/10.1002/cncr.24037)

    • Search Google Scholar
    • Export Citation
  • Ganepola GAP, Mazziotta RM, Weeresinghe D, Corner GA, Parish CJ, Chang DH, Tebbutt NC, Murone C, Ahmed N & Augenlicht LH et al. 2010 Gene expression profiling of primary and metastatic colon cancers identifies a reduced proliferative rate in metastatic tumors. Clinical and Experimental Metastasis 27 19. (https://doi.org/10.1007/s10585-009-9295-2)

    • Search Google Scholar
    • Export Citation
  • Gong Y, Chippada-Venkata UD & Oh WK 2014 Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers 6 12981327. (https://doi.org/10.3390/cancers6031298)

    • Search Google Scholar
    • Export Citation
  • Guarnieri V, Battista C, Muscarella LA, Bisceglia M, de Martino D, Baorda F, Maiello E, D’Agruma L, Chiodini I & Clemente C et al. 2012 CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cellular Oncology 35 411422. (https://doi.org/10.1007/s13402-012-0100-x)

    • Search Google Scholar
    • Export Citation
  • Hajjari M & Salavaty A 2015 HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biology and Medicine 12 19. (https://doi.org/10.7497/j.issn.2095-3941.2015.0006)

    • Search Google Scholar
    • Export Citation
  • Hammond E, Khurana A, Shridhar V & Dredge K 2014 The role of heparanase and sulfatases in the modification of heparan sulfate proteoglycans within the tumor microenvironment and opportunities for novel cancer therapeutics. Frontiers in Oncology 4 195. (https://doi.org/10.3389/fonc.2014.00195)

    • Search Google Scholar
    • Export Citation
  • Han B, Peng X, Cheng D, Zhu Y, Du J, Ju Li J & Yu X 2019 Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA-34a axis. Cancer Science 110 30893097. (https://doi.org/10.1111/cas.14133)

    • Search Google Scholar
    • Export Citation
  • Haven CJ, Howell VM, Eilers PHC, Dunne R, Takahashi M, van Puijenbroek M, Furge K, Kievit J, Tan MH & Fleuren GJ et al. 2004 Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype. Cancer Research 64 74057411. (https://doi.org/10.1158/0008-5472.CAN-04-2063)

    • Search Google Scholar
    • Export Citation
  • Haven CJ, van Puijenbroek M, Tan MH, Teh BT, Fleuren GJ, van Wezel T & Morreau H 2007 Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clinical Endocrinology 67 370376. (https://doi.org/10.1111/j.1365-2265.2007.02894.x)

    • Search Google Scholar
    • Export Citation
  • Henke E, Nandigama R & Ergün S 2019 Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Frontiers in Molecular Biosciences 6 160. (https://doi.org/10.3389/fmolb.2019.00160)

    • Search Google Scholar
    • Export Citation
  • Herszényi L, Hritz I, Lakatos G, Varga MZ & Tulassay Z 2012 The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. International Journal of Molecular Sciences 13 1324013263. (https://doi.org/10.3390/ijms131013240)

    • Search Google Scholar
    • Export Citation
  • Howell VM, Haven CJ, Kahnoski K, Khoo SK, Petillo D, Chen J, Fleuren GJ, Robinson BG, Delbridge LW & Philips J et al. 2003 HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. Journal of Medical Genetics 40 657663. (https://doi.org/10.1136/jmg.40.9.657)

    • Search Google Scholar
    • Export Citation
  • Howell VM, Gill A, Clarkson A, Nelson AE, Dunne R, Delbridge LW, Robinson BG, Teh BT, Gimm O & Marsh DJ 2009 Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 94 434441. (https://doi.org/10.1210/jc.2008-1740)

    • Search Google Scholar
    • Export Citation
  • Hu Y, Liao Q, Cao S, Gao X & Zhao Y 2016 Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis. Endocrine 54 612619. (https://doi.org/10.1007/s12020-016-0997-3)

    • Search Google Scholar
    • Export Citation
  • Hunt JL, Carty SE, Yim JH, Murphy J & Barnes L 2005 Allelic loss in parathyroid neoplasia can help characterize malignancy. American Journal of Surgical Pathology 29 10491055. (https://doi.org/10.1097/01.pas.0000166368.68459.99)

    • Search Google Scholar
    • Export Citation
  • Jiang T, Wei BJ, Zhang DX, Li L, Qiao GL, Yao XA, Chen ZW, Liu X & Du XY 2019 Genome-wide analysis of differentially expressed lncRNA in sporadic parathyroid tumors. Osteoporosis International 30 15111519. (https://doi.org/10.1007/s00198-019-04959-y)

    • Search Google Scholar
    • Export Citation
  • Juhlin CC, Nilsson IL, Lagerstedt-Robinson K, Stenman A, Bränström R, Tham E & Höög A 2019 Parafibromin immunostainings of parathyroid tumors in clinical routine: a near-decade experience from a tertiary center. Modern Pathology 32 10821094. (https://doi.org/10.1038/s41379-019-0252-6)

    • Search Google Scholar
    • Export Citation
  • Karaarslan S, Yurum FN, Kumbaraci BS, Pala EE, Sivrikoz ON, Akyildiz M & Bugdayci MH 2015 The role of parafibromin, galectin-3, HBME-1, and Ki-67 in the differential diagnosis of parathyroid tumors. Oman Medical Journal 30 421427. (https://doi.org/10.5001/omj.2015.84)

    • Search Google Scholar
    • Export Citation
  • Kim HK, Oh YL, Kim SH, Lee DY, Kang HC, Lee JI, Jang HW, Hur KY, Kim JH & Min YK et al. 2012 Parafibromin immunohistochemical staining to differentiate parathyroid carcinoma from parathyroid adenoma. Head and Neck 34 201206. (https://doi.org/10.1002/hed.21716)

    • Search Google Scholar
    • Export Citation
  • Kim GJ, Rhee H, Yoo JE, Ko JE, Lee JS, Kim H, Choi JS & Park YN 2014a Increased expression of CCN2, epithelial membrane antigen, and fibroblast activation protein in hepatocellular carcinoma with fibrous stroma showing aggressive behavior. PLoS ONE 9 e105094. (https://doi.org/10.1371/journal.pone.0105094)

    • Search Google Scholar
    • Export Citation
  • Kim NS, Lee HH, Jung CK & Jeon HM 2014b Versican expression in tumor epithelial cells is correlated with a good prognosis in gastric cancer. Anticancer Research 34 56135619.

    • Search Google Scholar
    • Export Citation
  • Krebs LJ, Shattuck TM & Arnold A 2005 HRPT2 mutational analysis of typical sporadic parathyroid adenomas. Journal of Clinical Endocrinology and Metabolism 90 50155017. (https://doi.org/10.1210/jc.2005-0717)

    • Search Google Scholar
    • Export Citation
  • Kytola S, Farnebo F, Obara T, Isola J, Grimelius L, Farnebo LO, Sandelin K & Larsson C 2000 Patterns of chromosomal imbalances in parathyroid carcinomas. American Journal of Pathology 157 579586. (https://doi.org/10.1016/S0002-9440(1064568-3)

    • Search Google Scholar
    • Export Citation
  • Law CW, Chen Y, Shi W & Smyth GK 2014 Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biology 15 R29. (https://doi.org/10.1186/gb-2014-15-2-r29)

    • Search Google Scholar
    • Export Citation
  • Lee JY, Eom EM, Kim DS, Ha-Lee YM & Lee DH 2003 Analysis of gene expression profiles of gastric normal and cancer tissues by SAGE. Genomics 82 7885. (https://doi.org/10.1016/s0888-7543(0300098-3)

    • Search Google Scholar
    • Export Citation
  • Lee HO, Mullins SR, Franco-Barraza J, Valianou M, Cukierman E & Cheng JD 2011 FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells. BMC Cancer 11 245. (https://doi.org/10.1186/1471-2407-11-245)

    • Search Google Scholar
    • Export Citation
  • Lee JY, Kim SY, Mo EY, Kim ES, Han JH, Maeng LS, Lee AH, Eun JW, Nam SW & Moon SD 2014 Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation. International Journal of Oncology 45 641650. (https://doi.org/10.3892/ijo.2014.2477)

    • Search Google Scholar
    • Export Citation
  • Li F, Wu X, Sun Z, Cai P, Wu L & Li D 2020 Fibroblast activation protein-α expressing fibroblasts promote lymph node metastasis in esophageal squamous cell carcinoma. OncoTargets and Therapy 13 81418148. (https://doi.org/10.2147/OTT.S257529)

    • Search Google Scholar
    • Export Citation
  • Li L, Zhang Z, Wang C, Miao L, Zhang J, Wang J, Jiao B & Zhao S 2014 Quantitative proteomics approach to screening of potential diagnostic and therapeutic targets for laryngeal carcinoma. PLoS ONE 9 e90181. (https://doi.org/10.1371/journal.pone.0090181)

    • Search Google Scholar
    • Export Citation
  • Li X, Chen T, Shi Q, Li J, Cai S, Zhou P, Zhong Y & Yao L 2015 Angiopoietin-like 4 enhances metastasis and inhibits apoptosis via inducing bone morphogenetic protein 7 in colorectal cancer cells. Biochemical and Biophysical Research Communications 467 128134. (https://doi.org/10.1016/j.bbrc.2015.09.104)

    • Search Google Scholar
    • Export Citation
  • Liu R, Li H, Liu L, Yu J & Ren X 2012 Fibroblast activation protein: a potential therapeutic target in cancer. Cancer Biology and Therapy 13 123129. (https://doi.org/10.4161/cbt.13.3.18696)

    • Search Google Scholar
    • Export Citation
  • Luhtala S, Staff S, Kallioniemi A, Tanner M & Isola J 2018 Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4-1 and NRDP1, in primary breast cancer. BMC Cancer 18 1045. (https://doi.org/10.1186/s12885-018-4917-1)

    • Search Google Scholar
    • Export Citation
  • Matulka M, Konopka A, Mroczko B, Pryczynicz A, Kemona A, Groblewska M, Sieskiewicz A & Olszewska E 2019 Expression and concentration of matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinases 1 in laryngeal squamous cell carcinoma. Disease Markers 2019 3136792 (https://doi.org/10.1155/2019/3136792)

    • Search Google Scholar
    • Export Citation
  • Morotti A, Forno I, Verdelli C, Guarnieri V, Cetani F, Terrasi A, Silipigni R, Guerneri S, Andrè V & Scillitani A et al. 2020 The oncosuppressors MEN1 and CDC73 are involved in lncRNA deregulation in human parathyroid tumors. Journal of Bone and Mineral Research 35 2423–2431. (https://doi.org/10.1002/jbmr.4154)

    • Search Google Scholar
    • Export Citation
  • Mota JM, Collier KA, Barros Costa RL, Taxter T, Kalyan A, Leite CA, Chae YK, Giles FJ & Carneiro BA 2017 A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer. Oncotarget 8 8928489306. (https://doi.org/10.18632/oncotarget.18467)

    • Search Google Scholar
    • Export Citation
  • Muscarella LA, Turchetti D, Fontana A, Baorda F, Palumbo O, La Torre A, De Martino D, Franco R, Losito NS & Repaci A et al. 2018 Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion. Oncotarget 9 2072120733. (https://doi.org/10.18632/oncotarget.25067)

    • Search Google Scholar
    • Export Citation
  • Novak D, Hüser L, Elton JJ, Umansky V, Altevogt P & Utikal J 2019 SOX2 in development and cancer biology. Seminars in Cancer Biology 18 3018530188. (https://doi.org/10.1016/j.semcancer.2019.08.007)

    • Search Google Scholar
    • Export Citation
  • Pandya C, Uzilov AV, Bellizzi J, Lau CY, Moe AS, Strahl M, Hamou W, Newman LC, Fink MY & Antipin Y et al. 2017 Genomic profiling reveals mutational landscape in parathyroid carcinomas. JCI Insight 2 e92061. (https://doi.org/10.1172/jci.insight.92061)

    • Search Google Scholar
    • Export Citation
  • Papadas A, Arauz G, Cicala A, Wiesner J & Asimakopoulos F 2020 Versican and versican-matrikines in cancer progression, inflammation, and immunity. Journal of Histochemistry and Cytochemistry 68 871885. (https://doi.org/10.1369/0022155420937098)

    • Search Google Scholar
    • Export Citation
  • Puré E & Blomberg R 2018 Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics. Oncogene 37 43434357. (https://doi.org/10.1038/s41388-018-0275-3)

    • Search Google Scholar
    • Export Citation
  • Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B & Samant RS et al. 2008 The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Medical Genomics 1 13. (https://doi.org/10.1186/1755-8794-1-13)

    • Search Google Scholar
    • Export Citation
  • Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W & Smyth GK 2015 Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43 e47. (https://doi.org/10.1093/nar/gkv007)

    • Search Google Scholar
    • Export Citation
  • Ryhänen EM, Leijon H, Metso S, Eloranta E, Korsoff P, Ahtiainen P, Kekäläinen P, Tamminen M, Ristamäki R & Knutar O et al. 2017 A nationwide study on parathyroid carcinoma. Acta Oncologica 56 9911003. (https://doi.org/10.1080/0284186X.2017.1306103)

    • Search Google Scholar
    • Export Citation
  • Sadowski SM, Pusztaszeri M, Brulhart-Meynet MC, Petrenko V, De Vito C, Sobel J, Delucinge-Vivier C, Kebebew E, Regazzi R & Philippe J et al. 2018 Identification of differential transcriptional patterns in primary and secondary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 103 21892198. (https://doi.org/10.1210/jc.2017-02506)

    • Search Google Scholar
    • Export Citation
  • Sevcnikar B, Schaffner I, Chuang CY, Gamon L, Paumann-Page M, Hofbauer S, Davies MJ, Furtmüller PG & Obinger C 2020 The leucine-rich repeat domain of human peroxidasin 1 promotes binding to laminin in basement membranes. Archives of Biochemistry and Biophysics 689 108443. (https://doi.org/10.1016/j.abb.2020.108443)

    • Search Google Scholar
    • Export Citation
  • Shao X, Lv N, Liao J, Long J, Xue R, Ai N, Xu D & Fan X 2019 Copy number variation is highly correlated with differential gene expression: a pan-cancer study. BMC Medical Genetics 20 175. (https://doi.org/10.1186/s12881-019-0909-5)

    • Search Google Scholar
    • Export Citation
  • Shen XH, Qi P & Du X 2015 Long non-coding RNAs in cancer invasion and metastasis. Modern Pathology 28 413. (https://doi.org/10.1038/modpathol.2014.75)

    • Search Google Scholar
    • Export Citation
  • Solano-Iturri JD, Beitia M, Errarte P, Calvete-Candenas J, Etxezarraga MC, Loizate A, Echevarria E, Badiola I & Larrinaga G 2020 Altered expression of fibroblast activation protein-α (FAP) in colorectal adenoma-carcinoma sequence and in lymph node and liver metastases. Aging 12 1033710358. (https://doi.org/10.18632/aging.103261)

    • Search Google Scholar
    • Export Citation
  • Sun W, Kuang XL, Liu YP, Tian LF, Yan XX & Xu W 2017 Crystal structure of the N-terminal domain of human CDC73 and its implications for the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Scientific Reports 7 15638. (https://doi.org/10.1038/s41598-017-15715-9)

    • Search Google Scholar
    • Export Citation
  • Tan MH, Morrison C, Wang P, Yang X, Haven CJ, Zhang C, Zhao P, Tretiakova MS, Korpi-Hyovalti E & Burgess JR et al. 2004 Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clinical Cancer Research 10 66296637. (https://doi.org/10.1158/1078-0432.CCR-04-0493)

    • Search Google Scholar
    • Export Citation
  • Tan MJ, Teo Z, Sng MK, Zhu P & Tan NS 2012 Emerging roles of angiopoietin-like 4 in human cancer. Molecular Cancer Research 10 677688. (https://doi.org/10.1158/1541-7786.MCR-11-0519)

    • Search Google Scholar
    • Export Citation
  • Thorsen SB, Christensen SLT, Würtz S, Lundberg M, Nielsen BS, Vinther L, Knowles M, Gee N, Fredriksson S & Møller S et al. 2013 Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study. BMC Cancer 13 98609. (https://doi.org/10.1186/1471-2407-13-598)

    • Search Google Scholar
    • Export Citation
  • Truran PP, Johnson SJ, Bliss RD, Lennard TWJ & Aspinall SR 2014 Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer. World Journal of Surgery 38 28452854. (https://doi.org/10.1007/s00268-014-2700-2)

    • 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 8798. (https://doi.org/10.1530/ERC-14-0161)

    • Search Google Scholar
    • Export Citation
  • Verdelli C, Avagliano L, Guarnieri V, Cetani F, Ferrero S, Vicentini L, Beretta E, Scillitani A, Creo P & Bulfamante GP et al. 2017 Expression, function, and regulation of the embryonic transcription factor TBX1 in parathyroid tumors. Laboratory Investigation 97 14881499. (https://doi.org/10.1038/labinvest.2017.88)

    • Search Google Scholar
    • Export Citation
  • Walker C, Mojares E & del Río Hernández A 2018 Role of extracellular matrix in development and cancer progression. International Journal of Molecular Sciences 19 30283058. (https://doi.org/10.3390/ijms19103028)

    • Search Google Scholar
    • Export Citation
  • Wang O, Wang C, Nie M, Cui Q, Guan H, Jiang Y, Li M, Xia W, Meng X & Xing X 2012 Novel HRPT2/CDC73 Gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas. PLoS ONE 7 e45567. (https://doi.org/10.1371/journal.pone.0045567)

    • Search Google Scholar
    • Export Citation
  • Wang RF, Zhang LH, Shan LH, Sun WG, Chai CC, Wu HM, Ibla JC, Wang LF & Liu JR 2013 Effects of the fibroblast activation protein on the invasion and migration of gastric cancer. Experimental and Molecular Pathology 95 350356. (https://doi.org/10.1016/j.yexmp.2013.10.008)

    • Search Google Scholar
    • Export Citation
  • Wang K, Ji W, Yu Y, Li Z, Niu X, Xia W & Lu S 2018 FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer. Oncogene 37 53405354. (https://doi.org/10.1038/s41388-018-0311-3)

    • Search Google Scholar
    • Export Citation
  • Wight TN 2017 Provisional matrix: a role for versican and hyaluronan. Matrix Biology 60 61 3856. (https://doi.org/10.1016/j.matbio.2016.12.001)

    • Search Google Scholar
    • Export Citation
  • Xu T, Zhang R, Dong M, Zhang Z, Li H, Zhan C & Li X 2019 Osteoglycin (OGN) inhibits cell proliferation and invasiveness in breast cancer via PI3K/Akt/mTOR signaling pathway. OncoTargets and Therapy 12 1063910650. (https://doi.org/10.2147/OTT.S222967)

    • Search Google Scholar
    • Export Citation
  • Yadav VK, Lee TY, Hsu JB, Huang HD, Yang WV & Chang TH 2020 Computational analysis for identification ofthe extracellular matrix molecules involved in endometrial cancer progression. PLoS ONE 15 e0231594. (https://doi.org/10.1371/journal.pone.0231594)

    • Search Google Scholar
    • Export Citation
  • Yang F, Gao Y, Geng J, Qu D, Han Q, Qi J & Chen G 2013 Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer. International Journal of Clinical and Experimental Pathology 6 28462854.

    • Search Google Scholar
    • Export Citation
  • Yu Q, Hardin H, Chu YH, Rehrauer W & Lloyd RV 2019 Parathyroid neoplasms: immunohistochemical characterization and long noncoding RNA (lncRNA) expression. Endocrine Pathology 30 96105. (https://doi.org/10.1007/s12022-019-9578-3)

    • Search Google Scholar
    • Export Citation
  • Zhang X, Hu Y, Wang M, Zhang R, Wang P, Cui M, Su Z, Gao X, Liao Q & Zhao Y 2019 Profiling analysis of long non-coding RNA and mRNA in parathyroid carcinoma. Endocrine-Related Cancer 26 163176. (https://doi.org/10.1530/ERC-18-0480)

    • Search Google Scholar
    • Export Citation
  • Zhao J, Hu Y, Liao Q, Niu Z, Xing X, Xia W & Zhao Y 2014 Gene identification of potential malignant parathyroid tumors phenotype in Chinese population. Endocrine Journal 61 597605. (https://doi.org/10.1507/endocrj.ej14-0023)

    • Search Google Scholar
    • Export Citation
  • Zhao J, Liu J, Wu N, Zhang H, Zhang S, Li L & Wang M 2020 ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer. Oncology Letters 20 24992505. (https://doi.org/10.3892/ol.2020.11768)

    • Search Google Scholar
    • Export Citation