{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:15Z","timestamp":1786978335772,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,1,17]],"date-time":"2011-01-17T00:00:00Z","timestamp":1295222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oral cancer is a highly aggressive malignancy with poor prognosis. This study examined the behaviour of fibroblast strains from normal oral mucosa, dysplastic epithelial tissue, and genetically stable (minimal copy number alterations\u2014CNA; minimal loss of heterozygosity\u2014LOH; wild\u2010type p53; wild\u2010type p16\n                    <jats:styled-content>\n                      $^{{\\rm INK4A}}$\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/>\n                    <\/jats:styled-content>\n                    ) and unstable (extensive CNA and LOH; inactivation of p53 and p16\n                    <jats:styled-content>\n                      $^{{\\rm INK4A}}$\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-2.gif\" xlink:title=\"equation image\"\/>\n                    <\/jats:styled-content>\n                    ) oral squamous cell carcinoma (OSCC). Fibroblasts from genetically unstable OSCC relative to the other fibroblast subtypes grew more slowly and stimulated the invasion of a non\u2010tumourigenic keratinocyte cell line into fibroblast\u2010rich collagen gels. To understand these findings, genome\u2010wide transcriptional profiles were generated using the GeneChip\n                    <jats:sup>\u00ae<\/jats:sup>\n                    cDNA whole transcript microarray platform. Principal component analysis showed that the fibroblasts could be distinguished according to the stage of tumour development. Tumour progression was associated with down\u2010regulation of cell cycle\u2010 and cytokinesis\u2010related genes and up\u2010regulation of genes encoding transmembrane proteins including cell adhesion molecules. Gene expression was validated in independent fibroblast strains using qRT\u2010PCR. Gene connectivity and interactome\u2010transcriptome associations were determined using a systems biology approach to interrogate the gene expression data. Clusters of gene signatures were identified that characterized genetically unstable and stable OSCCs relative to each other and to fibroblasts from normal oral mucosa. The expression of highly connected genes associated with unstable OSCCs, including those that encode \u03b1\u2010SMA and the integrin \u03b16, correlated with poor patient prognosis in an independent dataset of head and neck cancer. The results of this study demonstrate that fibroblasts from unstable OSCCs represent a phenotypically distinguishable subset that plays a major role in oral cancer biology. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2841","type":"journal-article","created":{"date-parts":[[2010,12,9]],"date-time":"2010-12-09T08:01:33Z","timestamp":1291881693000},"page":"459-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma"],"prefix":"10.1002","volume":"223","author":[{"given":"Kue 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