A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival

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...

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Bibliographic Details
Published in:Cancers 2021-11, Vol.13 (22), p.5737
Main Authors: 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.
Format: Article
Language:English
Subjects:
Algorithms
Biomarkers
Biopsy
CCL3 protein
CD38 antigen
Cellular biology
Cervical cancer
Cervix
Genes
Human papillomavirus
Immune response
Infections
Infiltration
Lck protein
Lesions
Medical prognosis
Medical research
Medical screening
Metastases
Patients
Transcriptomics
Tumors
Womens health
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13225737