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A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival.
Halle, Mari K; Munk, Ane Cecilie; Engesæter, Birgit; Akbari, Saleha; Frafjord, Astri; Hoivik, Erling A; Forsse, David; Fasmer, Kristine E; Woie, Kathrine; Haldorsen, Ingfrid S; Bertelsen, Bjørn I; Janssen, Emiel A M; Gudslaugsson, Einar; Krakstad, Camilla; Øvestad, Irene T.
Afiliação
  • Halle MK; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5053 Bergen, Norway.
  • Munk AC; Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway.
  • Engesæter B; Department of Obstetrics and Gynaecology, Sørlandet Hospital Kristiansand, 4604 Kristiansand, Norway.
  • Akbari S; Section for Cervical Cancer Screening, Cancer Registry of Norway, 0304 Oslo, Norway.
  • Frafjord A; Department of Pathology, Stavanger University Hospital, 4068 Stavanger, Norway.
  • Hoivik EA; Department of Pathology, Stavanger University Hospital, 4068 Stavanger, Norway.
  • Forsse D; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5053 Bergen, Norway.
  • Fasmer KE; Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway.
  • Woie K; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5053 Bergen, Norway.
  • Haldorsen IS; Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway.
  • Bertelsen BI; Section for Radiology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
  • Janssen EAM; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway.
  • Gudslaugsson E; Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway.
  • Krakstad C; Section for Radiology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
  • Øvestad IT; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway.
Cancers (Basel) ; 13(22)2021 Nov 16.
Article em En | MEDLINE | ID: mdl-34830895
The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were compared. L1000 mRNA data from a cervical cancer cohort was available for validation (n = 239). Transcriptomic analyses identified TDO2 (p = 0.004), CCL5 (p < 0.001), CCL3 (p = 0.04), CD38 (p = 0.02), and PRF1 (p = 0.005) as upregulated, and LCK downregulated (p = 0.01) in CIN3 regression as compared to persistent CIN3 lesions. From these, a gene signature predicting CIN3 regression with a sensitivity of 91% (AUC = 0.85) was established. Transcriptomic analyses revealed proliferation as significantly linked to persistent CIN3. Within the cancer cohort, high regression signature score associated with immune activation by Gene Set enrichment Analyses (GSEA) and immune cell infiltration by histopathological evaluation (p < 0.001). Low signature score was associated with poor survival (p = 0.007) and large tumors (p = 0.01). In conclusion, the proposed six-gene signature predicts CIN regression and favorable cervical cancer prognosis and points to common drivers in precursors and cervical cancer lesions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article