Search

Purpose: Currently, the associations between type-specific high-risk human papillomavirus (HR-HPV) viral loads and cervical lesions are still inconsistent. We aimed to assess the type-specific HR-HPV viral load as a risk triage indicator for development of high-grade squamous intraepithelial lesion or worse (≥HSIL)., Patients and Methods: A total of 19,446 women who underwent primary screening for cervical cancer using Cervista ® HR-HPV and cytology assays were enrolled. The viral loads of 1,396 HR-HPV-positive specimens confirmed by Cervista ® assay were detected by BioPerfectus Multiplex Real-Time PCR assay. The correlation between viral loads and cervical lesions was analyzed. The optimal cutoffs of individual HR-HPV viral loads used to predict ≥HSIL were determined from the receiver operating characteristic curve. A logistic regression model was used to analyze the relationship between covariates and the probability of ≥HSIL., Results: The viral loads of HPV-16, -31, -33, -52, and -58 were positively correlated with the severity of the cervical lesion, which was significantly elevated in patients with ≥HSIL, whereas those of HPV-18, -45, -56, -59, and other types were not. The optimal cutoffs of the log 10 -transformed viral loads for HPV-16, -31, -33, -52, and -58 in identifying ≥HSIL were 4.26, 4.46, 4.48, 4.36, and 4.26 copies per 10,000 cells, respectively. Furthermore, multivariate analysis indicated that type-specific viral loads of HPV-16, -31, -33, -52, and -58 exceeding the cutoffs could be independent risk factors for the incidence of ≥HSIL., Conclusion: The BioPerfectus Multiplex Real-Time PCR viral load assay provides viable triage for ≥HSIL when using appropriate cutoff levels., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms., Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells., Results: The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) ( P <0.05), and similar results were observed for ERRα protein levels. A higher ratio of ERa/ERRa was observed in ERα-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ERα-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both - exogenous XCT790 and endogenous siRNA-ERRα - can decrease the expression of ERRα, thereby inhibiting proliferation but promoting apoptosis in both ERα-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ERα-positive than ERα-negative cells, whereas the siRNA-ERRα exhibited higher proliferation-inhibition and apoptosis rates in the ERα-negative than in ERα-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERRα in all EC cells. Among them, the upregulated TFs organic cation transporter 3/4(Oct3/4), hepatic nuclear factor 4 (HNF4), HNF4 and chicken ovalbumin upstream TF (COUP-TF) as well as downregulated transcription factor EB (TFEB) were found to be statistically significant ( P <0.05)., Conclusion: Targeting ERRα provides a promising novel endocrine therapeutic strategy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.