A gene signature identifying CIN3 regression and cervical cancer survival
| Autor: | Emiel A. M. Janssen, Ingfrid S. Haldorsen, Bjørn I. Bertelsen, Saleha Akbari, Einar Gudslaugsson, Ane Cecilie Munk, Mari K. Halle, Camilla Krakstad, David Forsse, Kathrine Woie, Erling A. Hoivik, Birgit Engesæter, Irene T Øvestad, Kristine Eldevik Fasmer, Astri Frafjord |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty cervical cancer CD38 cervical intraepithelial neoplasia (CIN) Article immune activation CCL5 Transcriptome conization Internal medicine medicine prognostic biomarker Gene perforin RC254-282 HPV test Cervical cancer business.industry gene expression analyses Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Regression female genital diseases and pregnancy complications LCK Cohort business |
| Zdroj: | Cancers Cancers, Vol 13, Iss 5737, p 5737 (2021) Volume 13 Issue 22 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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