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dc.contributor.authorHalle, Mari Kyllesø
dc.contributor.authorSødal, Marte
dc.contributor.authorForsse, David Erik
dc.contributor.authorEngerud, Hilde Renate
dc.contributor.authorWoie, Kathrine
dc.contributor.authorLura, Njål Gjærde
dc.contributor.authorWagner-Larsen, Kari Strøno
dc.contributor.authorTrovik, Jone
dc.contributor.authorBertelsen, Bjørn
dc.contributor.authorHaldorsen, Ingfrid S.
dc.contributor.authorOjesina, Akinyemi I.
dc.contributor.authorKrakstad, Camilla
dc.date.accessioned2021-11-23T08:31:43Z
dc.date.available2021-11-23T08:31:43Z
dc.date.created2021-09-16T17:10:08Z
dc.date.issued2021
dc.identifier.issn0007-0920
dc.identifier.urihttps://hdl.handle.net/11250/2830881
dc.description.abstractBackground: Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease. Methods: Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort. Results: Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ). Conclusions: This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleA 10-gene prognostic signature points to LIMCH1 and HLA-DQB1 as important players in aggressive cervical cancer diseaseen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 the authorsen_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1038/s41416-021-01305-0
dc.identifier.cristin1935092
dc.source.journalBritish Journal of Canceren_US
dc.source.pagenumber1690-1698en_US
dc.identifier.citationBritish Journal of Cancer. 2021, 124 (10), 1690-1698.en_US
dc.source.volume124en_US
dc.source.issue10en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal