Search

Ying Wang,1,2,* Sai Han,1,* Xuewu You,1 Xuejiao Shi,3 Lu Liu,1 Yu Sun,1 Yana Ma,1 Qiuhong Qian,1 Hongli Liu,1 Baoxia Cui,1 Youzhong Zhang11Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Obstetrics and Gynecology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, People’s Republic of China; 3Department of Rheumatism and Immunology, Weihai Municipal Hospital, Weihai, Shandong 264200, People’s Republic of ChinaCorrespondence: Youzhong ZhangDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, People’s Republic of ChinaEmail zhangyouzhong@sdu.edu.cn*These authors contributed equally to this workBackground: It is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer.Methods: Bioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research.Results: We found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree (P=0.0266), indicating poor prognosis (P=0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro.Conclusion: LRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.Keywords: HPV, cervical cancer, LRP11, P16, cell cycle

Background: In China, cervical cancer is one of the most common gynecologic malignancies. Cervical cytology is an essential method for screening cervical cancer and cervical intraepithelial neoplasia (CIN), and the most common cytological abnormality result is atypical squamous cells of undetermined significance (ASC-US). Therefore, how to effectively deal with ASC-US cytology has become the focus of scholars. Objective: We aim to analyze the final histopathologic results, clinicopathologic significance and current rationale of ASC-US cytology. Methods: All patients with first ASC-US cytological reports who attended our gynecological outpatient clinic in Qilu Hospital of Shandong University during January 2010 to December 2015 were recruited to this study. The data were derived from clinical records and evaluated retrospectively. The results of age, High-Risk HPV (DNA) testing, colposcopy, and pathological outcomes were obtained. Directed biopsy was performed if there were any suspicious cervical lesions under colposcopy, while four quadrant biopsy and/or ECC were performed if no suspicious lesions were noted in colposcopies. Results: A total of 1246 patients diagnosed with ASC-US were involved in the final statistical analysis. Mean age of patients was 41.6 years and the age range between 40-49 years represented 38.52% of all ASC-US women in this study. All patients were evaluated for HPV (DNA) and positive percent for High-Risk HPV was (67.1%). According to the final histopathologic outcomes after ASC-US cytology, 15.6% and 1.1% of patients had ≥ CIN2+ and invasive carcinoma respectively. Patients with invasive carcinoma were associated with HPV16+ and HPV18+. The detection rate of ≥ CIN2+ among the ASC-US/High-Risk HPV+ group was (53.9%) with a negative-predictive-value (NPV) of 100%. Our findings showed that the final pathologic results of ≥ CIN2+ were consistent with colposcopy with a coincidence rate of (77%), and colposcopical impression sensitivity and specificity for ≥ CIN2+ was (91.1% and 96.1%) respectively. Conclusion: women with ASC-US have a wide range of final pathologic results, and it can be the initial warning of high-grade CIN or cervical cancer. In China, HPV (DNA) testing triage is a useful shunting measure for ASC-US patients, and an immediate colposcopy is a consequential strategy for dealing with ASC-US cytology to increase the detection rate of high-grade cervical lesions or invasive cancer.