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
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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
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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)