Background/Aims: Microarray screening had found BRAF-activated non-coding RNA (BANCR) was significantly upregulated in type 1 endometrial cancer (EC). This study aimed to assess the potential role of long non-coding RNA (lncRNA) BANCR in the pathogenesis and progression of type 1 EC. Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of BANCR in type 1 EC tissue, and analyze its clinical significance. In vitro, RNA interference (siRNA) was used to investigate the biological role of BANCR in type 1 EC. Results: qRT-PCR revealed that the expression of lncRNA BANCR was higher in type 1 EC (P<0.01). BANCR expression was significantly correlated with FIGO stage, pathological grade, myometrial invasion, and lymph node metastasis. The expression of BANCR was significantly correlated with that of MMP2/MMP1. In vitro, knockdown of BANCR significantly suppressed proliferation, migration, and invasion of Ishikawa and HEC-1A cells, and significantly inhibited the ERK/MAPK signaling pathway that decreased MMP2 and MMP1 expression. Conclusion: BANCR is highly expressed in type 1 EC tissue and promotes EC-cell proliferation, migration, and invasion by activating ERK/MAPK signaling pathway that regulates MMP2/MMP1 expression. BANCR is expected to become a prognostic marker and therapeutic target in type 1 EC.
Background/Aims: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved. Methods: Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p. Conclusions: CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy.
BackgroundWomen having multiple sex partners are reportedly at an increased risk of HPV infection. However, the prevalence and risk factors of HPV infection in female sex workers (FSWs) vary considerably across racial/ethnic, socioeconomic, and geographic groups. This study aimed to determine the prevalence and risk factors of HPV infection in FSWs in Northeast China.MethodsA total of 309 FSWs identified and approached through a local police office and 1000 healthy subjects from a single factor undergoing annual gynecological examinations in Shenyang were recruited. A liquid-based ThinPrep Pap test and the Hybrid Capture II-based high-risk HPV DNA test, with or without a colposcopic examination, were performed on both FSWs and control subjects. Data on HPV infection and histological and cytological lesions of the cervix were obtained and analyzed. A questionnaire survey was administered to all 309 FSWs with their socio-demographic and behavioral information collected. The association of various socio-demographic and behavioral variables with HPV infection was assessed.ResultsHPV was significantly more prevalent in FSWs (61.90 %) than in healthy control subjects (21.00 %) (P < 0.01), so were cervical lesions (P < 0.01). HPV prevalence in our sample of FSWs fell in the upper range of reported values in FSWs across different countries, and was similar to that for FSWs in the southeast Chinese city of Huzhou but higher than that for FSWs in southwest China, Guangxi, as compared with data from other studies within China. HPV infection in FSWs was significantly associated with the age at first sexual intercourse (OR 0.699, 95 % CI 0.492–0.992) and post-menopause (OR 2.928, 95 % CI 1.099–7.800) (P < 0.05).ConclusionsFSWs are at a substantially high risk of HPV infection and cervical dysplasia development as compared with healthy control subjects in Shenyang, China. Age of first sexual intercourse and post-menopause are two independent risk factors for HPV infection in this special group of population. Intensified and coordinated efforts from government, public health sector, communities and families are needed to reduce the risk of HPV infection in this specific group of population.
The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.
Endometrial carcinoma (EC) is the fifth widely occurring malignant neoplasm among women all over the world. However, there is still lacking efficacy indicators for EC’s prognosis. Here, we analyzed two databases including an RNA-sequencing-based TCGA dataset and a microarray-based GSE106191. After normalizing the raw data, we identified 114 common genes with upregulation and 308 common genes with downregulation in both the TCGA and GSE106191 databases. Bioinformatics analysis showed that the differently expressed genes in EC were related to the IL17 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway. Furthermore, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and generated a signature featuring 17 prognosis-related genes (MAL2, ANKRD22, METTL7B, IL32, ERFE, OAS1, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2) and found that it could predict OS in EC patients. The further analysis showed that OAS1, MAL2, ANKRD22, METTL7B, and IL32 were significantly upregulated in EC samples after comparison with normal samples. However, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2 were significantly downregulated in EC samples in comparison with normal samples. And correlation analysis showed that our results showed that the expressions of 17 prognosis-related hub genes were significantly correlated based on Pearson correlation. We here offer a newly genetic biomarker for the prediction of EC patients’ prognosis.
Abstract. B-Raf proto-oncogene, serine/threonine kinase (BRAF) has previously been identified as a candidate target gene in endometriosis. Wild-type and mutated BRAF serve important roles in different diseases. The aim of the present study was to explore BRAF mutation, the mRNA and protein expression of wild-type BRAF ( wt BRAF) in endometriosis, and the association between the expression levels of wt BRAF and the predicted transcription factor cAMP responsive element binding protein 1 (CREB1). In the present study, BRAF mutation was detected using Sanger sequencing among 30 ectopic and matched eutopic endometrium samples of patients with endometriosis as well as 25 normal endometrium samples, and no BRAF mutation was detected in exons 11 or 15. A region of ~2,000 bp upstream of the BRAF gene was then screened using NCBI and UCSC databases, and CREB1 was identified as a potential transcription factor of BRAF by analysis with the JASPAR and the TRANSFAC databases. Quantitative polymerase chain reaction was used to analysis the mRNA expression levels of wt BRAF and CREB1, and the corresponding protein expression levels were evaluated using immunohistochemistry and western blot analysis. The results revealed that the mRNA and protein expression levels of wt BRAF and CREB1 were significantly upregulated in the eutopic endometrial tissues of patients with endometriosis compared with normal endometrial tissues (P<0.05) and no significant difference in wt BRAF and CREB1 levels was detected between the ectopic and eutopic endometrium (P>0.05). In addition, correlation analysis revealed that the protein expression of CREB1 was positively correlated with the transcript level and protein expression of wt BRAF. It is reasonable to speculate that CREB1 may activate the transcription of wt BRAF through directly binding to its promoter, increasing BRAF expression and regulating the cell proliferation, migration and invasion of endometriosis.
We evaluated the ability of our two laparotomy-based models to predict optimal primary debulking surgery (PDS) and long-term outcomes of stage IIIC epithelial ovarian cancer (EOC). Data of 400 IIIC EOC patients who underwent laparotomy were retrospectively analyzed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated for 10 parameters. The parameters with a specificity ≥75%, PPV ≥50%, and NPV ≥50% were included in the final predictive index value (PIV) model. Peritoneal cancer index (PCI) was calculated summarizing lesion size scores (LSSs) of 13 regions. Receiver operating characteristic (ROC) curve was used to assessed the predictive value of PIV and PCI for optimal PDS. Univariate and multivariate analyses were performed to assess the prognostic value of PIV and PCI. After PDS, 223 (55.8%) patients with RD ≤1 cm had longer progression-free survival (PFS) and overall survival (OS) than patients with RD >1 cm (PFS: 22.4 vs. 15.4 months, respectively; P < 0.001 and OS: 48.6 vs. 35.6 months; P < 0.001). PCI better predicted optimal PDS than PIV (The area under the curve of ROC: PCI 0.79 vs. PIV 0.75). The predictive value of PIV and PCI models was verified using another cohort of 77 patients. And PIV and PCI models were demonstrated to be more powerful than the published laparoscopy-based predictive index (LPS-PI) model. Patients with a PIV ≥14 were more likely to undergo suboptimal PDS with a specificity of 100%. The median PFS and OS of patients with PIV < 3 were significantly longer than patients with PIV > 3 (PFS: 19.5 vs. 16.3 months, P = 0.007; OS: 46.1 vs. 37.0 months, P = 0.009). The median PFS and OS of patients with the PCI < 17.5 were significantly longer than patients with the PCI > 17.5 (PFS: 22.9 vs. 14.5 months, P < 0.001; OS: 54.3 vs. 31.5 months, P < 0.001). PCI could better predict optimal PDS compared with PIV. PCI was an independent prognostic factor for long-term outcome of IIIC EOC patients.
Background: To investigate the survival outcomes of abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy (LRH), and vaginal-assisted laparoscopic radical hysterectomy (VALRH) in the treatment of cervical cancer patients.Methods: This was a retrospective study. We collected the clinical data of 654 patients with cervical cancer (406 ARH, 172 LRH, and 76 VALRH), then compared the effects of different surgical methods on recurrence and survival.Results: Total overall survival (OS) were no significant differences in three groups (P>0.05). Total diseasefree survival (DFS) was significantly higher in ARH group than in LRH group [hazard ratio (HR) =2.8, 95% confidence interval (CI): 1.199-3.607, P=0.004]; however, there were no significant differences between the VALRH (94.7%) and ARH (93.3%) groups. Subgroup stratification analysis showed that the overall recurrence rate in LRH group was significantly higher than that of the ARH groups for patients with a tumor size from ≥2 to <4 cm, negative postoperative lymph nodes, and no postoperative adjuvant therapy (all P<0.05). However, in the subgroup with tumor sizes of ≥2, <4, and ≥4 cm, no matter whether the lymph nodes were positive or not, and those with no postoperative supplementary adjuvant therapy, LRH was associated with a significantly higher local pelvic recurrence rate than ARH (all P<0.05). No significant differences between VALRH and ARH in any of the subgroup analyses (all P>0.05). A Cox analysis indicated that LRH increased the risk of overall and local pelvic recurrence after surgery compared with ARH (HR =2.338, 95% CI: 1.186-4.661, P=0.014; HR =10.313, 95% CI: 2.839-37.460, P<0.001); however, no significant difference between VALRH and ARH (all P>0.05). Sensitivity analysis of surgeons did not change the conclusions.Conclusions: Our analyses showed that the local pelvic recurrence rates and overall recurrence rates of LRH were significantly higher than ARH. VALRH could avoid tumor intraperitoneal exposure and achieve the same tumor prognosis as open surgery. By improving the standardization of minimally invasive surgery for early cervical cancer and paying close attention to the tumor-free concept, minimally invasive radical hysterectomy may achieve the same tumor outcome as open surgery.
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