{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:12:55Z","timestamp":1747195975033,"version":"3.40.5"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors (hESCC) by using RNA sequencing and NanoString profiling. Objectives were to investigate differences in RNA signaling between hESCC and sporadic ESCC (sESCC), and to look for early malignant changes in non-neoplastic esophageal tissue of HL survivors (hNN-tissue). We analyzed material of 26 hESCC cases, identified via the Dutch pathology registry (PALGA) and 17 sESCC cases from one academic institute and RNA sequencing data of 44 sESCC cases from TCGA. Gene expression profiles for the NanoString panel PanCancer IO 360 were obtained from 16\/26 hESCC and four hNN-tissue, while non-neoplastic squamous tissue of four sporadic cases (sNN-tissue) served as reference profile. Hierarchical clustering, differential expression and pathway analyses were performed. Overall, the molecular profiles of hESCC and sESCC were similar. There was increased immune, HMGB1 and ILK signaling compared to sNN-tissue. The profiles of hNN-tissue were distinct from sNN-tissue, indicating early field effects in the esophagus of HL survivors. The BRCA1 pathway was upregulated in hESCC tissue, compared to hNN tissue. Analysis of expression profiles reveals overlap between hESCC and sESCC, and differences between hESCC and its surrounding hNN-tissue. Further research is required to validate our results and to investigate whether the changes observed in hNN-tissue are already detectable before development of hESCC. In the future, our findings could be used to improve hESCC patient management.<\/jats:p>","DOI":"10.1371\/journal.pone.0243178","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T18:37:02Z","timestamp":1608575822000},"page":"e0243178","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gene expression profiles of esophageal squamous cell cancers in Hodgkin lymphoma survivors versus sporadic cases"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-7986","authenticated-orcid":true,"given":"Berbel L. M.","family":"Ykema","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanne J. M.","family":"Hoefnagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisanne S.","family":"Rigter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liudmila L.","family":"Kodach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit A.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora E.","family":"van Leeuwen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hina N.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petur","family":"Snaebjornsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berthe M. P.","family":"Aleman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annegien","family":"Broeks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sybren L.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth K.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kausilia K.","family":"Krishnadath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique E.","family":"van Leerdam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of GIOCA-OES","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"issue":"12","key":"pone.0243178.ref001","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1200\/JCO.2006.09.0936","article-title":"Long-term solid cancer risk among 5-year survivors of Hodgkin's lymphoma","volume":"25","author":"D.C. Hodgson","year":"2007","journal-title":"J Clin Oncol"},{"issue":"31","key":"pone.0243178.ref002","doi-asserted-by":"crossref","first-page":"4096","DOI":"10.1200\/JCO.2011.34.8268","article-title":"Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study","volume":"29","author":"A.J. Swerdlow","year":"2011","journal-title":"J Clin Oncol"},{"issue":"26","key":"pone.0243178.ref003","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMoa1505949","article-title":"Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma","volume":"373","author":"M. Schaapveld","year":"2015","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0243178.ref004","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/cam4.1922","article-title":"Overall and disease-specific survival of Hodgkin lymphoma survivors who subsequently developed gastrointestinal cancer","volume":"8","author":"L.S. Rigter","year":"2019","journal-title":"Cancer Med"},{"issue":"10","key":"pone.0243178.ref005","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.3324\/haematol.2014.108258","article-title":"Risk of esophageal cancer following radiotherapy for Hodgkin lymphoma","volume":"99","author":"L.M. Morton","year":"2014","journal-title":"Haematologica"},{"issue":"7636","key":"pone.0243178.ref006","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nature20805","article-title":"Integrated genomic characterization of oesophageal carcinoma","volume":"541","author":"Cancer Genome Atlas Research, N","year":"2017","journal-title":"Nature"},{"issue":"10","key":"pone.0243178.ref007","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/ng.3076","article-title":"Genetic landscape of esophageal squamous cell carcinoma","volume":"46","author":"Y.B. Gao","year":"2014","journal-title":"Nat Genet"},{"issue":"2","key":"pone.0243178.ref008","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/path.1260","article-title":"Barrett's adenocarcinomas resemble adenocarcinomas of the gastric cardia in terms of chromosomal copy number changes, but relate to squamous cell carcinomas of the distal oesophagus with respect to the presence of high-level amplifications","volume":"199","author":"M.M. Weiss","year":"2003","journal-title":"J Pathol"},{"issue":"2","key":"pone.0243178.ref009","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ajhg.2015.12.013","article-title":"Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma","volume":"98","author":"C. Cheng","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"5","key":"pone.0243178.ref010","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/ng.2935","article-title":"Genomic and molecular characterization of esophageal squamous cell carcinoma","volume":"46","author":"D.C. Lin","year":"2014","journal-title":"Nat Genet"},{"issue":"10","key":"pone.0243178.ref011","doi-asserted-by":"crossref","first-page":"e0139808","DOI":"10.1371\/journal.pone.0139808","article-title":"An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma","volume":"10","author":"G. Sawada","year":"2015","journal-title":"PLoS One"},{"issue":"7498","key":"pone.0243178.ref012","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature13176","article-title":"Identification of genomic alterations in oesophageal squamous cell cancer","volume":"509","author":"Y. Song","year":"2014","journal-title":"Nature"},{"issue":"2","key":"pone.0243178.ref013","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ijrobp.2009.09.004","article-title":"Radiation-associated breast tumors display a distinct gene expression profile","volume":"76","author":"A. Broeks","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"6","key":"pone.0243178.ref014","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/carcin\/bgr064","article-title":"A transcriptome signature distinguished sporadic from postradiotherapy radiation-induced sarcomas","volume":"32","author":"N.S. Hadj-Hamou","year":"2011","journal-title":"Carcinogenesis"},{"issue":"3","key":"pone.0243178.ref015","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1136\/gutjnl-2016-312608","article-title":"Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment","volume":"67","author":"L.S. Rigter","year":"2018","journal-title":"Gut"},{"issue":"12","key":"pone.0243178.ref016","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/s41588-019-0525-5","article-title":"The mutational footprints of cancer therapies","volume":"51","author":"O. Pich","year":"2019","journal-title":"Nat Genet"},{"issue":"6","key":"pone.0243178.ref017","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1093\/carcin\/bgi356","article-title":"Specific TP53 mutation pattern in radiation-induced sarcomas","volume":"27","author":"N. Gonin-Laurent","year":"2006","journal-title":"Carcinogenesis"},{"issue":"22","key":"pone.0243178.ref018","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1056\/NEJMoa1112088","article-title":"Preoperative chemoradiotherapy for esophageal or junctional cancer","volume":"366","author":"P. van Hagen","year":"2012","journal-title":"N Engl J Med"},{"issue":"12","key":"pone.0243178.ref019","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nrc1749","article-title":"Mechanisms of therapy-related carcinogenesis","volume":"5","author":"J.M. Allan","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"pone.0243178.ref020","doi-asserted-by":"crossref","first-page":"e0117070","DOI":"10.1371\/journal.pone.0117070","article-title":"Genetic features of metachronous esophageal cancer developed in Hodgkin's lymphoma or breast cancer long-term survivors: an exploratory study","volume":"10","author":"E. Boldrin","year":"2015","journal-title":"PLoS One"},{"key":"pone.0243178.ref021","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.radonc.2018.09.017","article-title":"Volume effects of radiotherapy on the risk of second primary cancers: A systematic review of clinical and epidemiological studies","author":"N. Journy","year":"2019","journal-title":"Radiother Oncol"},{"issue":"3","key":"pone.0243178.ref022","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/carcin\/21.3.397","article-title":"Radiation carcinogenesis","volume":"21","author":"J.B. Little","year":"2000","journal-title":"Carcinogenesis"},{"issue":"8","key":"pone.0243178.ref023","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/gm268","article-title":"Genetics and genomics of radiotherapy toxicity: towards prediction","volume":"3","author":"C.M. West","year":"2011","journal-title":"Genome Med"},{"issue":"1","key":"pone.0243178.ref024","first-page":"19","article-title":"Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive","volume":"29","author":"M. Casparie","year":"2007","journal-title":"Cell Oncol"},{"issue":"1","key":"pone.0243178.ref025","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/14737159.2017.1268533","article-title":"NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics","volume":"17","author":"H.F. Tsang","year":"2017","journal-title":"Expert Rev Mol Diagn"},{"issue":"2","key":"pone.0243178.ref026","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1053\/j.gastro.2017.08.023","article-title":"Epidemiology of Esophageal Squamous Cell Carcinoma","volume":"154","author":"C.C. Abnet","year":"2018","journal-title":"Gastroenterology"},{"issue":"1","key":"pone.0243178.ref027","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s40425-018-0367-1","article-title":"-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA)","volume":"6","author":"P. Danaher","year":"2018","journal-title":"J Immunother Cancer"},{"issue":"1","key":"pone.0243178.ref028","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41467-017-00842-8","article-title":"Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism","volume":"8","author":"G. Antoniali","year":"2017","journal-title":"Nat Commun"},{"issue":"20","key":"pone.0243178.ref029","first-page":"e151","article-title":"NanoStringDiff: a novel statistical method for differential expression analysis based on NanoString nCounter data","volume":"44","author":"H. Wang","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0243178.ref030","unstructured":"NanostringNorm. Available: https:\/\/CRAN.R-project.org\/package = NanoStringNorm [Accessed August 2019]."},{"issue":"12","key":"pone.0243178.ref031","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"M.I. Love","year":"2014","journal-title":"Genome Biol"},{"issue":"59","key":"pone.0243178.ref032","first-page":"289","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","year":"1995","journal-title":"J.R. Statist. Soc. B"},{"key":"pone.0243178.ref033","unstructured":"Integuity Target Explorer. Available: https:\/\/targetexplorer.ingenuity.com\/pathway\/ING\/ING:civ#!\/api\/rest\/v1\/client\/searchPathwayNodes?pathwayId=ING:civ&rows=0&facetLimit=5000&responseType=default [Accessed August 2019]."},{"key":"pone.0243178.ref034","unstructured":"Ingenuity Target Explorer. Available: https:\/\/targetexplorer.ingenuity.com\/pathway\/ING\/ING:1nili#!\/api\/rest\/v1\/client\/searchPathwayNodes?pathwayId=ING:1nili&rows=0&facetLimit=5000&responseType=default [Accessed August 2019]."},{"key":"pone.0243178.ref035","unstructured":"Ingenuity Target Explorer. Available: https:\/\/targetexplorer.ingenuity.com\/pathway\/ING\/ING:46ckb#!\/api\/rest\/v1\/client\/searchPathwayNodes?pathwayId=ING:46ckb&rows=0&facetLimit=5000&responseType=default [Accessed August 2019]."},{"issue":"13","key":"pone.0243178.ref036","first-page":"3087","article-title":"Loss of DNA mismatch repair in acquired resistance to cisplatin","volume":"56","author":"S. Aebi","year":"1996","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0243178.ref037","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.0959-9673.2006.00464.x","article-title":"Accelerated growth of intestinal tumours after radiation exposure in Mlh1-knockout mice: evaluation of the late effect of radiation on a mouse model of HNPCC","volume":"87","author":"Y. Tokairin","year":"2006","journal-title":"Int J Exp Pathol"},{"key":"pone.0243178.ref038","unstructured":"Ingenuity Target Explorer. Available: https:\/\/targetexplorer.ingenuity.com\/pathway\/ING\/ING:3ddup#!\/api\/rest\/v1\/client\/searchPathwayNodes?pathwayId=ING:3ddup&rows=0&facetLimit=5000&responseType=default [Accessed August 2019]."},{"issue":"8","key":"pone.0243178.ref039","first-page":"1727","article-title":"A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications","volume":"63","author":"B.J. Braakhuis","year":"2003","journal-title":"Cancer Res"},{"issue":"66","key":"pone.0243178.ref040","first-page":"371","article-title":"Field cancerization in Barrett's esophagus","volume":"12","author":"S.S. Zeki","year":"2011","journal-title":"Discov Med"},{"issue":"1","key":"pone.0243178.ref041","doi-asserted-by":"crossref","first-page":"14756","DOI":"10.1038\/s41598-017-15145-7","article-title":"Comparison of Transcriptomic Platforms for Analysis of Whole Blood from Ebola-Infected Cynomolgus Macaques","volume":"7","author":"E. Speranza","year":"2017","journal-title":"Sci Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T18:37:53Z","timestamp":1608575873000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243178"}},"subtitle":[],"editor":[{"given":"Amanda Ewart","family":"Toland","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0243178","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2020,12,21]]}}}