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CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(09): 682-689
DOI: 10.1055/s-0041-1735301
Original Articles
Lower Genital Tract Diseases

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

Vias de ativação de IFN-alfa em pacientes com Neoplasia Intraepitelial Cervical (NIC)
Nelson Ranieri Tirone 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Carolina Guissoni Campos 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Kézia Jesus Aguiar Ferreira 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Léticia Montes Stark 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Jéssica Ferreira Vieira 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Eddie Fernando Cândido Murta 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
2   Department of Gynecology and Obstetrics, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
,
Márcia Antoniazi Michelin 
1   Instituto de Pesquisa em Oncologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
3   Discipline of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
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Abstract

Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer.

Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells.

Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes.

Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

Resumo

Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA)

Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′-oligoadenilato sintetase (2'5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico.

Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos.

Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.

Keywords

interferon receptors - cervical intraepithelial neoplasia - interferon alpha

Palavras-chave

receptores de interferon - neoplasia intraepitelial cervical - interferon alfa

Contributors

Conception and design of the study: Michelin MA and Murta EFC. Data collection and performance of the experiments: Campos CG, Stark LM, Tirone NR. Statistical analysis and writing of the paper: Ferreira KJA, Vieira JF, and Stark LM. All authors were contributed with the conduction and interpretation of the data.




Publication History

Received: 10 December 2020

Accepted: 02 August 2021

Article published online:
20 October 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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