Retracted: Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Mei Mei Guan, Qun Xian Rao, Miao Ling Huang, Li Juan Wang, Shao Dan Lin, Qing Chen, Chang Hao Liu. Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines. Med Sci Monit, 2019; 25: 8131-8141. DOI: 10.12659/MSM.916292.

Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

BACKGROUND Worldwide, mortality from cervical cancer in women remains high. This study aimed to investigate the expression of long noncoding RNA (lncRNA) TP73-AS1, microRNA-329-3p (miRNA-329-3p), and the SMAD2 gene and their regulatory relationships in human cervical cancer tissue and cervical cancer cell lines. MATERIAL AND METHODS Cervical cancer tissue samples (n=30) and normal control cervical tissues were studied. Cell proliferation and migration were investigated in HeLa and SiHa human cervical cancer cells using the MTT assay, crystal violet staining, wound healing assay, and the transwell assay. Expression of lncRNA TP73-AS1 and the SMAD2 gene were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Enrichment of miR-329-3p was measured using the RNA immunoprecipitation assay (RIPA). Targeting relationships between TP73-AS1, miR-329-3p, and SMAD2 were identified using the dual-luciferase reporter assay. A subcutaneous xenograft model was established, tumor size was measured, and SMAD2 expression was detected using immunohistochemistry. RESULTS LncRNA TP73-AS1 was overexpressed in cervical cancer tissues and cells and was associated with reduced expression of miR-329-3p. Down-regulation of lncRNA TP73-AS1 inhibited cell proliferation, migration and invasion and increased miR-329-3p expression. Expression of SMAD2 down-regulated miR-329-3p and was associated with increased expression of TP73-AS1. LncRNA TP73-AS1 knockdown resulted in miR-329-3p silencing. In tumor xenografts, expression of TP73-AS1 reduced the tumor volume and down-regulated the expression levels of the SMAD2 gene. CONCLUSIONS LncRNA TP73-AS1 promoted proliferation of cervical cancer cell lines by targeting miR-329-3p to regulate the expression of the SMAD2 gene. A regulatory network was formed between lncRNA TP73-AS1, miR-329-3p, and SMAD2.

Pretreatment glycemic control status is an independent prognostic factor for cervical cancer patients receiving neoadjuvant chemotherapy for locally advanced disease.

BACKGROUND: To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC). METHODS: A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A1c (HbA1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: In total, 388 patients were included and had a median follow-up time of 39 months (range: 4-67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA1c < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA1c ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA1c ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA1c ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT. CONCLUSIONS: Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC.

The added value of fasting blood glucose to serum squamous cell carcinoma antigen for predicting oncological outcomes in cervical cancer patients receiving neoadjuvant chemotherapy followed by radical hysterectomy.

OBJECTIVE: To determine the combination of fasting blood glucose (FBG) with squamous cell carcinoma antigen (SCCA) assessments in the prediction of tumor responses to chemotherapy and pretreatment prognostication among patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC). METHODS: Data of 347 LACC patients were retrospectively reviewed. Receiver operating characteristic (ROC) curves were constructed, and areas under the curves (AUCs) were compared to evaluate the ability to predict complete response (CR) following NACT. Patients were stratified into groups with low and high levels of SCCA and FBG and combined into low- or high-SCCA and low- or high-FBG groups. Cox regression analysis was performed to identify determinants of recurrence-free survival (RFS) and overall survival (OS). RESULTS: The AUCs were 0.70, 0.68, and 0.66 for SCCA, FBG, and a combination of SCCA and FBG for predicting CR following NACT, respectively; however, the differences among AUCs were not significant (P = .496). Pretreatment SCCA and FBG levels were identified as independent predictors of RFS and OS. The high-SCCA/high-FBG group showed significantly worse prognosis than the low-SCCA/low-FBG group. After adjusting for other variables, high-SCCA/high-FBG remained independently associated with an increased risk of tumor recurrence and death. CONCLUSION: SCCA, FBG, and a combination of SCCA and FBG could acceptably predict CR following NACT. Pretreatment SCCA and FBG levels were independent prognostic factors. The combination of SCCA and FBG levels refined the prognostic stratification of LACC patients, which allowed the group of patients with the highest risk of recurrence and death to be identified.

A modified triple incision technique for women with locally advanced vulvar cancer: a description of the technique and outcomes.

OBJECTIVE: Women with locally advanced vulvar carcinoma have an excellent chance of a cure by undergoing a radical vulvectomy with an "en bloc" inguinofemoral lymphadenectomy, but the morbidity associated this surgical approach is substantial. To achieve an outcome comparable with the traditional radical method in terms of oncologic safety, and an improved post-operative quality of life, we modified the classic triple-incision technique and suggested it as an alternative for these patients. The aim of this study was to report this new technique. STUDY DESIGN: Between January 2004 and November 2009, 24 patients with clinical stage T2 (≥ 4 cm) or T3 invasive vulvar cancer underwent surgical treatment with our modified triple incision technique. Their clinical and surgical complications and follow-up data were retrospectively reviewed. RESULTS: The post-surgical complications were as follows: lymphoedema in 45.8%, wound breakdown in 20.8% and cellulitis in 8.3%. After a median follow-up of 35.5 months, three (12.5%) patients developed a recurrence in the skin bridge (2/24, 8.3%) or lungs (1/24, 4.2%). All patients suffering from skin bridge recurrences were salvaged by local re-resection. Four (16.7%) cases of death were noted: three (12.5%) patients died of non-cancer-related diseases and one (4.2%) died from a multifocal pulmonary metastasis; no evidence of vulvar or groin disease was observed at these patients' last follow-up. CONCLUSION: The modified triple-incision technique described in this preliminary study appears to be safe, feasible and tolerable for patients with a locally advanced vulvar cancer, and offers an acceptable morbidity.

Expression and functional role of ALDH1 in cervical carcinoma cells.

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.