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To eradicate CSCs, parallels can be drawn from signalling modules that orchestrate pluripotency. Notch-Hedgehog hyperactivation are seen in CSCs, yet, not much is known about their conserved roles in tumour progression across cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Employing a comparative approach involving 21 cancers, we uncovered clinically-relevant, pan-cancer drivers of Notch and Hedgehog. GISTIC datasets were used to evaluate copy number alterations. Receiver operating characteristic and Cox regression were employed for survival analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a Notch-Hedgehog signature of 13 genes exhibiting high frequencies of somatic amplifications leading to transcript overexpression. The signature successfully predicted patients at risk of death in five cancers (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092278): glioma (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001), clear cell renal cell (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0022), papillary renal cell (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.00099), liver (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.014) and stomach (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.011). The signature was independent of other clinicopathological parameters and offered an additional resolution to stratify similarly-staged tumours. High-risk patients exhibited features of stemness and had more hypoxic tumours, suggesting that hypoxia may influence CSC behaviour. Notch-Hedgehog\n                      <jats:sup>+<\/jats:sup>\n                      CSCs had an immune privileged phenotype associated with increased regulatory T cell function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study will set the stage for exploring adjuvant therapy targeting the Notch-Hedgehog axis to help optimise therapeutic regimes leading to successful CSC elimination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-019-0572-9","type":"journal-article","created":{"date-parts":[[2019,9,15]],"date-time":"2019-09-15T19:02:42Z","timestamp":1568574162000},"page":"666-678","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Aberrations in Notch-Hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion"],"prefix":"10.1038","volume":"121","author":[{"given":"Wai Hoong","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvina G.","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"572_CR1","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1158\/1535-7163.MCT-11-1040","volume":"11","author":"M Maugeri-Sacc\u00e0","year":"2012","unstructured":"Maugeri-Sacc\u00e0, M., Bartucci, M. & De Maria, R. 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