ADAR1 overexpression is associated with cervical cancer progression and angiogenesis

Diagnostic Pathology, Jan 2017

Background This study aimed to assess the role of RNA-dependent adenosine deaminase (ADAR1) in cervical squamous cell carcinoma occurrence and progression. Methods ADAR1 expression levels in stage IA and stage IIA cervical squamous cell carcinoma (group A), cervical intraepithelial neoplasia (CIN) specimens (group B), as well as normal and inflamed cervical tissue samples (group C) were assessed by immunohistochemistry. Clinical and pathological data of cervical squamous cell carcinoma patients undergoing surgery were retrospectively evaluated. Chi-square test, comparative analysis of survival curve, disease-free survival and COX risk assessment method were used to understand the association of ADAR1 with the occurrence and progression and prognostic significance of cervical squamous cell carcinoma. Results ADAR1 is expressed in the cytoplasm and nuclei. The expression level was high in squamous cell carcinoma tissues (81.18%), while relatively low in the CIN group (21.56%). And there was no expression in non-cancerous tissues. The differences between them were statistically significant using P < 0.05 as criterion. One-factor analysis revealed that ADAR1 was significantly correlated with tumor diameter, horizontal diffusion diameter, vascular invasion, parametrial invasion, vaginal involvement, and pathologically diagnostic criteria for perineural invasion (PNI). Meanwhile, the overall survival rate of ADAR1 positive patients was significantly lower compared with that of patients with no ADAR1 expression (P < 0.05). Analysis also showed that disease-free survival time of ADAR1 positive patients was shorter than that of ADAR1 negative patients, and the difference was significant (P < 0.01). Finally, COX risk assessment showed that parametrical invasion had independent prognostic factors for overall survival of squamous cell carcinoma. Conclusions Results indicated that ADAR1 might play an important role in the occurrence, progression and prognosis of cervical squamous cancer.

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ADAR1 overexpression is associated with cervical cancer progression and angiogenesis

Chen et al. Diagnostic Pathology ADAR1 overexpression is associated with cervical cancer progression and angiogenesis Ying Chen 0 2 He Wang 0 Wenyi Lin 1 Ping Shuai 3 0 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University , Chengdu 610041, Sichuan , China 1 Department of Pathology, Sichuan Province, Chengdu Women's and Children's Central Hospital , Chengdu 610091 , China 2 Department of Obstetrics and Gynecology, Sichuan Province, Chengdu Women's and Children's Central Hospital , Chengdu 610091, Sichuan , China 3 Department Physical Examination, Sichuan People's Hospital , Chengdu 610072, Sichuan , China Background: This study aimed to assess the role of RNA-dependent adenosine deaminase (ADAR1) in cervical squamous cell carcinoma occurrence and progression. Methods: ADAR1 expression levels in stage IA and stage IIA cervical squamous cell carcinoma (group A), cervical intraepithelial neoplasia (CIN) specimens (group B), as well as normal and inflamed cervical tissue samples (group C) were assessed by immunohistochemistry. Clinical and pathological data of cervical squamous cell carcinoma patients undergoing surgery were retrospectively evaluated. Chi-square test, comparative analysis of survival curve, disease-free survival and COX risk assessment method were used to understand the association of ADAR1 with the occurrence and progression and prognostic significance of cervical squamous cell carcinoma. Results: ADAR1 is expressed in the cytoplasm and nuclei. The expression level was high in squamous cell carcinoma tissues (81.18%), while relatively low in the CIN group (21.56%). And there was no expression in non-cancerous tissues. The differences between them were statistically significant using P < 0.05 as criterion. One-factor analysis revealed that ADAR1 was significantly correlated with tumor diameter, horizontal diffusion diameter, vascular invasion, parametrial invasion, vaginal involvement, and pathologically diagnostic criteria for perineural invasion (PNI). Meanwhile, the overall survival rate of ADAR1 positive patients was significantly lower compared with that of patients with no ADAR1 expression (P < 0.05). Analysis also showed that disease-free survival time of ADAR1 positive patients was shorter than that of ADAR1 negative patients, and the difference was significant (P < 0.01). Finally, COX risk assessment showed that parametrical invasion had independent prognostic factors for overall survival of squamous cell carcinoma. Conclusions: Results indicated that ADAR1 might play an important role in the occurrence, progression and prognosis of cervical squamous cancer. Adenosine deaminase acting on RNA1; Cervical squamous cancer; Risk factor - Background Cervical carcinoma is the second most common malignant tumor in women around the world, and the first malignancy affecting females in developing countries. Indeed, about half a million women are diagnosed yearly with cervical cancer worldwide [1], with a mortality rate of 9%. In China, the number of new cases of cervical squamous cell carcinoma each year is 130,000, which accounts for 28% of newly diagnosed cases globally. And the mortality rate is 14%, which is higher compared with that obtained in other developing countries. For a long time, the studies of cancer mechanism had been greatly focused on the mechanism of DNA imbalance. Recently, we found that tumorigenesis might be caused by the process of RNA transcription, in which RNA editing enzyme played an important role. RNA editing is widespread in the evolutionary process [2]. It refers to RNA modifications and processing after the transcription of DNA into RNA. The edited RNA molecules may be translated to completely different proteins compared to their transcribed DNA sequences, hereby changing the genetic information [3–7]. Studies have shown that ADAR1 © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. is a RNA-dependent adenosine deaminase, with highest expression in tumor cells. It mainly plays a role of RNA editing to change A into G in chronic myelocytic leukemia [8–10], thereby changing the normal physiological structures and functions of proteins. In addition, ADAR1 plays an important role in laryngeal squamous cell carcinoma, and tends to promote its occurrence and progression [11]. However, relevant studies on cervical squamous cell carcinoma have not been reported previously. In (...truncated)


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Ying Chen, He Wang, Wenyi Lin, Ping Shuai. ADAR1 overexpression is associated with cervical cancer progression and angiogenesis, Diagnostic Pathology, 2017, pp. 12, 12, DOI: 10.1186/s13000-017-0600-0