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Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes

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Abstract

Celiac disease (CD) is a risk factor for developing small-bowel carcinoma with a 14-fold higher risk compared with general population. As small-bowel carcinomas associated with CD (CD-SBCs) are extremely rare, very few molecular data are available about their pathogenesis, and information about their transcriptomic profiling is lacking. We generated RNA-seq data on 13 CD-SBCs, taken from the largest well-characterized series published so far, collected by the Small Bowel Cancer Italian Consortium, and compared the tumor transcriptional signatures with the four Consensus Molecular Subtypes (CMS) of colorectal carcinoma by applying the “CMS classifier.” CpG Island Methylator Phenotype (CIMP) was evaluated using methylation-sensitive multiple ligation-dependent probe amplification. Up to 12 of 13 cancers fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e., subtypes 1 and 4. The first and predominant subset was commonly microsatellite unstable, and exhibited CIMP and high CD3+ and CD8+ T cell infiltration. Moreover, it showed increased expression of genes associated with T helper 1 and natural killer cell infiltration, as well as upregulation of apoptosis, cell cycle progression, and proteasome pathways. By contrast, cancers falling in subtype 4 showed prominent transforming growth factor-β activation and were characterized by complement-associated inflammation, matrix remodeling, cancer-associated stroma production, and angiogenesis. Parallel histologic and histochemical analysis confirmed such tumor subtyping. In conclusion, two molecular subtypes have been consistently identified in our series of CD-SBCs, a microsatellite instability-immune and a mesenchymal subtype, the former likely associated with an indolent and the latter with a worse tumor behavior.

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References

  1. Di Sabatino A, Corazza GR (2009) Coeliac disease. Lancet 373:1480–1493. https://doi.org/10.1016/S0140-6736(09)60254-3

    Article  PubMed  Google Scholar 

  2. Dube C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, Sampson M, Zhang L, Yazdi F, Mamaladze V, Pan I, Macneil J, Mack D, Patel D, Moher D (2005) The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology 128:S57–S67. https://doi.org/10.1053/j.gastro.2005.02.014

    Article  PubMed  Google Scholar 

  3. Aparicio T, Zaanan A, Svrcek M, Laurent-Puig P, Carrere N, Manfredi S, Locher C, Afchain P (2014) Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis 46:97–104. https://doi.org/10.1016/j.dld.2013.04.013

    Article  PubMed  Google Scholar 

  4. Han Y, Chen W, Li P, Ye J (2015) Association between coeliac disease and risk of any malignancy and gastrointestinal malignancy: a meta-analysis. Medicine (Baltimore) 94:e1612. https://doi.org/10.1097/MD.0000000000001612

    Article  Google Scholar 

  5. Howdle PD, Jalal PK, Holmes GK, Houlston RS (2003) Primary small-bowel malignancy in the UK and its association with coeliac disease. QJM 96:345–353. https://doi.org/10.1093/qjmed/hcg058

    Article  CAS  PubMed  Google Scholar 

  6. Bruno CJ, Batts KP, Ahlquist DA (1997) Evidence against flat dysplasia as a regional field defect in small bowel adenocarcinoma associated with celiac sprue. Mayo Clin Proc 72:320–322. https://doi.org/10.1016/S0025-6196(11)63330-2

    Article  CAS  PubMed  Google Scholar 

  7. Rampertab SD, Forde KA, Green PH (2003) Small bowel neoplasia in coeliac disease. Gut 52:1211–1214. https://doi.org/10.1136/gut.52.8.1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Potter DD, Murray JA, Donohue JH, Burgart LJ, Nagorney DM, van Heerden JA, Plevak MF, Zinsmeister AR, Thibodeau SN (2004) The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease. Cancer Res 64:7073–7077. https://doi.org/10.1158/0008-5472.CAN-04-1096

    Article  CAS  PubMed  Google Scholar 

  9. Diosdado B, Buffart TE, Watkins R, Carvalho B, Ylstra B, Tijssen M, Bolijn AS, Lewis F, Maude K, Verbeke C, Nagtegaal ID, Grabsch H, Mulder CJ, Quirke P, Howdle P, Meijer GA (2010) High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin Cancer Res 16:1391–1401. https://doi.org/10.1158/1078-0432.CCR-09-1773

    Article  CAS  PubMed  Google Scholar 

  10. Alvi MA, McArt DG, Kelly P, Fuchs MA, Alderdice M, McCabe CM, Bingham V, McGready C, Tripathi S, Emmert-Streib F, Loughrey MB, McQuaid S, Maxwell P, Hamilton PW, Turkington R, James JA, Wilson RH, Salto-Tellez M (2015) Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility. Oncotarget 6:20863–20874. https://doi.org/10.18632/oncotarget.4576

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vanoli A, Di Sabatino A, Furlan D, Klersy C, Grillo F, Fiocca R, Mescoli C, Rugge M, Nesi G, Fociani P, Sampietro G, Ardizzone S, Luinetti O, Calabro A, Tonelli F, Volta U, Santini D, Caio G, Giuffrida P, Elli L, Ferrero S, Latella G, Ciardi A, Caronna R, Solina G, Rizzo A, Ciacci C, D’Armiento FP, Salemme M, Villanacci V, Cannizzaro R, Canzonieri V, Reggiani Bonetti L, Biancone L, Monteleone G, Orlandi A, Santeusanio G, Macciomei MC, D’Inca R, Perfetti V, Sandri G, Silano M, Florena AM, Giannone AG, Papi C, Coppola L, Usai P, Maccioni A, Astegiano M, Migliora P, Manca R, Martino M, Trapani D, Cerutti R, Alberizzi P, Riboni R, Sessa F, Paulli M, Solcia E, Corazza GR (2017) Small bowel carcinomas in coeliac or Crohn’s disease: clinico-pathological, molecular, and prognostic features. A Study From the Small Bowel Cancer Italian Consortium. J Crohns Colitis 11:942–953. https://doi.org/10.1093/ecco-jcc/jjx031

    Article  PubMed  Google Scholar 

  12. Vanoli A, Di Sabatino A, Martino M, Klersy C, Grillo F, Mescoli C, Nesi G, Volta U, Fornino D, Luinetti O, Fociani P, Villanacci V, D’Armiento FP, Cannizzaro R, Latella G, Ciacci C, Biancone L, Paulli M, Sessa F, Rugge M, Fiocca R, Corazza GR, Solcia E (2017) Small bowel carcinomas in celiac or Crohn’s disease: distinctive histophenotypic, molecular and histogenetic patterns. Mod Pathol 30:1453–1466. https://doi.org/10.1038/modpathol.2017.40

    Article  CAS  PubMed  Google Scholar 

  13. Bijlsma MF, Sadanandam A, Tan P, Vermeulen L (2017) Molecular subtypes in cancers of the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 14:333–342. https://doi.org/10.1038/nrgastro.2017.33

    Article  CAS  PubMed  Google Scholar 

  14. Network CGAR (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209. https://doi.org/10.1038/nature13480

    Article  CAS  Google Scholar 

  15. Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa EMF, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356. https://doi.org/10.1038/nm.3967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautes-Fridman C, Fridman WH, de Reynies A (2016) Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol 17:218. https://doi.org/10.1186/s13059-016-1070-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Trinh A, Trumpi K, De Sousa EMF, Wang X, de Jong JH, Fessler E, Kuppen PJ, Reimers MS, Swets M, Koopman M, Nagtegaal ID, Jansen M, Hooijer GK, Offerhaus GJ, Kranenburg O, Punt CJ, Medema JP, Markowetz F, Vermeulen L (2017) Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry. Clin Cancer Res 23:387–398. https://doi.org/10.1158/1078-0432.CCR-16-0680

    Article  CAS  PubMed  Google Scholar 

  18. Tarallo R, Giurato G, Bruno G, Ravo M, Rizzo F, Salvati A, Ricciardi L, Marchese G, Cordella A, Rocco T, Gigantino V, Pierri B, Cimmino G, Milanesi L, Ambrosino C, Nyman TA, Nassa G, Weisz A (2017) The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Genome Biol 18:189. https://doi.org/10.1186/s13059-017-1321-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21. https://doi.org/10.1093/bioinformatics/bts635

    Article  CAS  PubMed  Google Scholar 

  20. Anders S, Pyl PT, Huber W (2015) HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166–169. https://doi.org/10.1093/bioinformatics/btu638

    Article  CAS  PubMed  Google Scholar 

  21. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https://doi.org/10.1186/s13059-014-0550-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS (2007) Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample. J Mol Diagn 9:305–314. https://doi.org/10.2353/jmoldx.2007.060170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Furlan D, Sahnane N, Mazzoni M, Pastorino R, Carnevali I, Stefanoli M, Ferretti A, Chiaravalli AM, La Rosa S, Capella C (2013) Diagnostic utility of MS-MLPA in DNA methylation profiling of adenocarcinomas and neuroendocrine carcinomas of the colon-rectum. Virchows Arch 462:47–56. https://doi.org/10.1007/s00428-012-1348-2

    Article  CAS  PubMed  Google Scholar 

  24. Satow R, Inagaki S, Kato C, Shimozawa M, Fukami K (2017) Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells. Cancer Sci 108:2405–2412. https://doi.org/10.1111/cas.13419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li L, Yan LH, Manoj S, Li Y, Lu L (2017) Central role of CEMIP in tumorigenesis and its potential as therapeutic target. J Cancer 8:2238–2246. https://doi.org/10.7150/jca.19295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Matheu A, Collado M, Wise C, Manterola L, Cekaite L, Tye AJ, Canamero M, Bujanda L, Schedl A, Cheah KS, Skotheim RI, Lothe RA, Lopez de Munain A, Briscoe J, Serrano M, Lovell-Badge R (2012) Oncogenicity of the developmental transcription factor Sox9. Cancer Res 72:1301–1315. https://doi.org/10.1158/0008-5472.CAN-11-3660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Roche KC, Gracz AD, Liu XF, Newton V, Akiyama H, Magness ST (2015) SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine. Gastroenterology 149(1553-1563):e1510. https://doi.org/10.1053/j.gastro.2015.07.004

    Article  CAS  Google Scholar 

  28. Panarelli NC, Vaughn CP, Samowitz WS, Yantiss RK (2015) Sporadic microsatellite instability-high colon cancers rarely display immunohistochemical evidence of Wnt signaling activation. Am J Surg Pathol 39:313–317. https://doi.org/10.1097/PAS.0000000000000380

    Article  PubMed  Google Scholar 

  29. Senger S, Sapone A, Fiorentino MR, Mazzarella G, Lauwers GY, Fasano A (2015) Celiac disease histopathology recapitulates hedgehog downregulation, consistent with wound healing processes activation. PLoS One 10:e0144634. https://doi.org/10.1371/journal.pone.0144634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ma F, Ye H, He HH, Gerrin SJ, Chen S, Tanenbaum BA, Cai C, Sowalsky AG, He L, Wang H, Balk SP, Yuan X (2016) SOX9 drives WNT pathway activation in prostate cancer. J Clin Invest 126:1745–1758. https://doi.org/10.1172/JCI78815

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sun L, Mathews LA, Cabarcas SM, Zhang X, Yang A, Zhang Y, Young MR, Klarmann KD, Keller JR, Farrar WL (2013) Epigenetic regulation of SOX9 by the NF-kappaB signaling pathway in pancreatic cancer stem cells. Stem Cells 31:1454–1466. https://doi.org/10.1002/stem.1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fernandez-Jimenez N, Castellanos-Rubio A, Plaza-Izurieta L, Irastorza I, Elcoroaristizabal X, Jauregi-Miguel A, Lopez-Euba T, Tutau C, de Pancorbo MM, Vitoria JC, Bilbao JR (2014) Coregulation and modulation of NFkappaB-related genes in celiac disease: uncovered aspects of gut mucosal inflammation. Hum Mol Genet 23:1298–1310. https://doi.org/10.1093/hmg/ddt520

    Article  CAS  PubMed  Google Scholar 

  33. Maiuri MC, De Stefano D, Mele G, Fecarotta S, Greco L, Troncone R, Carnuccio R (2003) Nuclear factor kappa B is activated in small intestinal mucosa of celiac patients. J Mol Med (Berl) 81:373–379. https://doi.org/10.1007/s00109-003-0440-0

    Article  CAS  Google Scholar 

  34. Castellanos-Rubio A, Santin I, Martin-Pagola A, Irastorza I, Castano L, Vitoria JC, Bilbao JR (2010) Long-term and acute effects of gliadin on small intestine of patients on potentially pathogenic networks in celiac disease. Autoimmunity 43:131–139. https://doi.org/10.3109/08916930903225229

    Article  CAS  PubMed  Google Scholar 

  35. Di Sabatino A, Lenti MV, Giuffrida P, Vanoli A, Corazza GR (2015) New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract. Autoimmun Rev 14:1161–1169. https://doi.org/10.1016/j.autrev.2015.08.004

    Article  CAS  PubMed  Google Scholar 

  36. Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, Cortina C, Morral C, Barcelo C, Tosi S, Riera A, Attolini CS, Rossell D, Sancho E, Batlle E (2015) Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 47:320–329. https://doi.org/10.1038/ng.3225

    Article  CAS  PubMed  Google Scholar 

  37. Isella C, Terrasi A, Bellomo SE, Petti C, Galatola G, Muratore A, Mellano A, Senetta R, Cassenti A, Sonetto C, Inghirami G, Trusolino L, Fekete Z, De Ridder M, Cassoni P, Storme G, Bertotti A, Medico E (2015) Stromal contribution to the colorectal cancer transcriptome. Nat Genet 47:312–319. https://doi.org/10.1038/ng.3224

    Article  CAS  PubMed  Google Scholar 

  38. Bergmann F, Singh S, Michel S, Kahlert C, Schirmacher P, Helmke B, Von Knebel DM, Kloor M, Blaker H (2010) Small bowel adenocarcinomas in celiac disease follow the CIM-MSI pathway. Oncol Rep 24:1535–1539. https://doi.org/10.3892/or_00001015

    Article  CAS  PubMed  Google Scholar 

  39. Giuffrida P, Vanoli A, Arpa G, Bonometti A, Luinetti O, Solcia E, Corazza GR, Paulli M, Di Sabatino A (2018) Small bowel carcinomas associated with immune-mediated intestinal disorders: the current knowledge. Cancers (Basel):11. https://doi.org/10.3390/cancers11010031

  40. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:563–567. https://doi.org/10.1038/nature14011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357:409–413. https://doi.org/10.1126/science.aan6733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank all the Collaborators of the “Small Bowel Cancer Italian Consortium.”

Funding

This study was supported by the University of Insubria (to Prof. Furlan, FAR project 2016-2017), the Italian Association for Cancer Research (AIRC Grant: IG-17426), and Regione Campania (“La Campania lotta contro il cancro” project Rare-Plat-Net, CUP: B63D18000380007; and project GENOMAeSALUTE, CUP: B41C17000080007) and Genomix4Life to Prof. Weisz. This research was also supported by a grant of the Italian Ministry of Education, University and Research (MIUR), to the Department of Molecular Medicine of the University of Pavia under the initiative “Dipartimenti di Eccellenza” (2018–2022) to Prof. Marco Paulli and by Fondazione IRCCS Policlinico San Matteo to Dr. Ombretta Luinetti. A.S. is a PhD student of the Research Doctorate in “Sciences and Biomedical Technologies–XXXI Cycle,” University Roma 3.

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Author notes

  1. Francesca Rizzo and Alessandro Vanoli contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, Salerno, Italy

    Francesca Rizzo, Antonio Rinaldi, Assunta Sellitto & Alessandro Weisz

  2. Medical Genomics Program, Department of Onco-Haematology SS. Giovanni di Dio e Ruggi d’Aragona University Hospital, University of Salerno, Salerno, Italy

    Francesca Rizzo & Alessandro Weisz

  3. Department of Molecular Medicine, University of Pavia and IRCCS San Matteo Hospital Foundation, Pavia, Italy

    Alessandro Vanoli, Giovanni Arpa, Ombretta Luinetti, Marco Paulli & Enrico Solcia

  4. Unit of Pathology, Dept. of Medicine and Surgery and Research Center for the Study of Hereditary and Familial Tumors, University of Insubria, Via Rossi 9, 21100, Varese, Italy

    Nora Sahnane, Roberta Cerutti, Davide Trapani, Fausto Sessa & Daniela Furlan

  5. Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Salerno, Italy

    Carolina Ciacci

  6. Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Umberto Volta

  7. Institute of Pathology, Spedali Civili, Brescia, Italy

    Vincenzo Villanacci

  8. Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Florence, Italy

    Antonio Calabrò

  9. Department of Internal Medicine, University of Pavia and IRCCS San Matteo Hospital Foundation, Pavia, Italy

    Antonio Di Sabatino

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  1. Francesca Rizzo
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  2. Alessandro Vanoli
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Correspondence to Daniela Furlan.

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Declaration of Helsinki and its revision and was approved by the Ethics Committee of the IRCCS San Matteo Hospital Foundation, Italy (no. 20140018113, on 22nd September 2014).

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The authors have no conflicts of interest

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Rizzo, F., Vanoli, A., Sahnane, N. et al. Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes. Virchows Arch 476, 711–723 (2020). https://doi.org/10.1007/s00428-019-02675-w

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