Survival Of Cervical Cancer Patients Research Articles

LncRNA SNHG7 contributes to cell proliferation, invasion and prognosis of cervical cancer.

Long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of lncRNA SNHG7 in cervical cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of lncRNA SNHG7 in cervical cancer and to explore the possible underlying mechanism. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA SNHG7 in 60 cervical cancer tissues and adjacent normal tissues. Cell Counting Kit-8 (CCK-8) and transwell assays were used to study the effects of lncRNA SNHG7 on the proliferation and invasion of cervical cancer cells, respectively. Furthermore, Western blot was used to detect the expression levels of proteins in the epithelial-mesenchymal transition (EMT) process. LncRNA SNHG7 expression increased significantly in cervical cancer tissues. The inhibition of lncRNA SNHG7 expression markedly inhibited cervical cell proliferation and invasion. Meanwhile, the inhibition of lncRNA SNHG7 resulted in the increased protein expression level of E-cadherin, and decreased protein expressions of N-cadherin and Vimentin. In addition, the survival time of patients with high expression of lncRNA SNHG7 was remarkably shortened. LncRNA SNHG7 contributes to cell proliferation and invasion of cervical cancer. Moreover, SNHG7 has emerged as an independent and significant factor associated with poor survival of cervical cancer patients.

A Network Topology Approach in Survival Analysis

Network topology can be used to simplify the complexity of the data sets. We are exploring its function in performing survival analysis to identify the most important factor that contributed to the survival time from diagnosis to death. This technique has the potential to illustrate easily some types of complex interactions in data set. Then, based on those interactions, the most important factor in survival analysis will be identified. In this paper, the interpretation of that network topology will be delivered by using centrality measures. A case study of the survival time for cervical cancer patients will be presented and discussed. Based on network topology, the most important factors that influence the survival of cervical cancer patients will be identified.

The effect of the population-based cervical cancer screening program on 5-year survival in cervical cancer patients in Lower Silesia.

Poland is considered among the European countries with an average incidence of cervical cancer (CC; about 3,000-3,500/year) and at the same time with high mortality (5-year survival rate - 55.2%). For this reason, in 2006 Poland introduced a Population-Based Cervical Cancer Prevention and Early Detection Program addressed to women aged 25-59 years, in which a cytological test is carried out every 3 years. The aim of the study was to assess the changes in the curability of CC patients brought by the introduction of the Screening Program in the Lower Silesian voivodeship and to identify the subpopulation of women for whom activities aimed at increasing adherence rates must be intensified. The 5-year relative survival in 3,586 CC patients from 2000-2010 registered in the Lower Silesian Cancer Registry was analyzed. In the Lower Silesian voivodeship, a 55.1% 5-year survival rate was recorded in 2000-2004 and 70.5% in 2010. The highest increase in 5-year relative survival rates was found in rural communities (from 53.1% in 2000-2004 to 77.7% in 2010) and in Wrocław (56.8% and 74.2%, respectively). In the study group, the number of patients with invasive CC (C53) detected in the local stage of the disease increased systematically from 61.5% in 2000-2004 to 74.3% in 2010. The introduction of the population-based screening program improved the curability rate in CC patients in the Lower Silesian voivodeship. In order to maintain the recent positive trends, further education should be continued, and activities aimed at increasing adherence to screening tests should be intensified, especially in urban-rural communities.

Knockdown of METTL14 inhibits the growth and invasion of cervical cancer

Background: Increasing evidence has revealed that N6-methyladenosine (m6A) modification is implicated in multiple biological functions in mammals. Methyltransferase-like 14 (METTL14), an important component of m6A modification, has been reported to play important roles in the pathogenesis of acute myeloid leukaemia and hepatocellular carcinoma metastasis. However, its role in cervical cancer remains unclear. Methods: Expression of METTL14 was knocked down by shRNA-METTL14 interference in HPV-positive and HPV-negative cervical cancer cell lines SiHa and C33a. CCK8, colony formation, wound-healing, and Transwell assays were performed to evaluate the effects of METTL14 knockdown on the proliferation, migration and invasion abilities of SiHa and C33a cells. Flow cytometry analysis was utilized to detect cell cycle distribution, and the expression of related proteins was examined by western blot analysis. Results: Bioinformatics analysis demonstrated that up-regulation of METTL14 acted as an adverse prognostic factor for overall survival in cervical cancer patients. We demonstrated that down-regulation of METTL14 inhibited the proliferation, migration and invasion abilities of SiHa and C33a cells. Moreover, silencing METTL14 induced cell cycle arrest in cervical cancer cells. METTL14 knockdown suppressed the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylation of Akt and mTOR, and the expression of downstream apoptosis-related proteins was also impacted. Conclusions: In conclusion, these data suggest an important oncogenic role of METTL14 in the growth and invasion of both HPV-positive and HPV-negative cervical cancer cells.

Knockdown of METTL14 inhibits the growth and invasion of cervical cancer.

BackgroundIncreasing evidence has revealed that N6-methyladenosine (m6A) modification is implicated in multiple biological functions in mammals. Methyltransferase-like 14 (METTL14), an important component of m6A modification, has been reported to play important roles in the pathogenesis of acute myeloid leukaemia and hepatocellular carcinoma metastasis. However, its role in cervical cancer remains unclear.MethodsExpression of METTL14 was knocked down by shRNA-METTL14 interference in HPV-positive and HPV-negative cervical cancer cell lines SiHa and C33a. CCK8, colony formation, wound-healing, and Transwell assays were performed to evaluate the effects of METTL14 knockdown on the proliferation, migration and invasion abilities of SiHa and C33a cells. Flow cytometry analysis was utilized to detect cell cycle distribution, and the expression of related proteins was examined by western blot analysis.ResultsBioinformatics analysis demonstrated that up-regulation of METTL14 acted as an adverse prognostic factor for overall survival in cervical cancer patients. We demonstrated that down-regulation of METTL14 inhibited the proliferation, migration and invasion abilities of SiHa and C33a cells. Moreover, silencing METTL14 induced cell cycle arrest in cervical cancer cells. METTL14 knockdown suppressed the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylation of Akt and mTOR, and the expression of downstream apoptosis-related proteins was also impacted.ConclusionsIn conclusion, these data suggest an important oncogenic role of METTL14 in the growth and invasion of both HPV-positive and HPV-negative cervical cancer cells.

LINC00511 is associated with the malignant status and promotes cell proliferation and motility in cervical cancer.

LINC00511 is a newly identified lncRNA that is up-regulated in many types of human cancers and may serve as an oncogenic lncRNA. However, there was no report about the role of LINC00511 in cervical cancer. Therefore, we investigated the clinical value of LINC00511 in cervical cancer patients via analyzing the correlation between LINC00511 expression and clinicopathological features. Moreover, we performed loss-of-function study to estimate the effect of LINC00511 on cervical cancer cell proliferation, migration, and invasion. In our study, we found LINC00511 expression levels were increased in cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cell line, respectively. High LINC00511 expression was correlated with advanced clinical stage, large tumor size, histological type of adenocarcinoma, and present lymph node metastasis, distant metastasis, and poor overall survival in cervical cancer patients. The in vitro studies indicated that knockdown of LINC00511 inhibited cervical cancer cell proliferation, migration, and invasion. In conclusion, LINC00511 acts as oncogenic lncRNA in cervical cancer, and may be a novel biomarker and potential therapeutic target for cervical cancer patients.

Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis

Circular RNAs (circRNAs) are a novel group of noncoding RNAs characterized by a covalently closed loop. An increasing evidence suggests that deregulated circRNAs exert their essential regulatory roles in oncogenesis. However, little is explored on the biological role of novel circRNAs in cervical cancer (CC) progression. In the present study, we analyzed two GSE microarrays to screen for CC-specific circRNAs and found two circRNAs both expressed in CC cells and tissues. Among them, circ_0005576 was significantly overexpressed in both CC tissues and cell lines. Furthermore, upregulated circ_0005576 was positively associated with advanced FIGO stage, lymph node metastasis, but was negatively related with overall survival of CC patients. Additionally, circ_0005576 knockdown induced a suppressed cell growth, colony formation and metastasis of HeLa and SiHa cells. Mechanistically, circ 0005576 was mainly located in the cytoplasm and served as a sponge of miR-153-3p to increase kinesin family member 20A (KIF20A) expression. Rescue assays further validated the effects of circ_0005576/miR-153-3p/KIF20A axis on CC proliferation, migration and invasion. In conclusion, our research reveals a novel circ_0005576/miR-153-3p/KIF20A axis promoting CC progression, which may suggest a new insight into the pathogenesis of CC.

TP73 is a credible biomarker for predicting clinical progression and prognosis in cervical cancer patients.

Tumor protein p73 (TP73) has been reported to be dysregulated in various types of human cancer and associated with clinical progression and outcome. Owing to the lack of reports on the correlation between TP73 protein expression and clinicopathologic features of cervical cancer, the aim of our research was to explore the clinical and prognostic significance of TP73 protein expression in cervical cancer patients. In our study, TP73 protein expression was detected by immunochemistry in 118 paraffin-embedded cervical cancer tissue specimens and 40 paraffin-embedded normal cervical epithelium tissue specimens. In the results, we found cervical cancer tissues exhibited high TP73 expression in comparison with normal cervical epithelium tissues, which was consistent with the expression status of TP73 in The Cancer Genome Atlas (TCGA) database. Furthermore, we analyzed the relationships between TP73 expression and clinicopathologic features through using the chi-square test or Fisher’s exact test, and found high expression of TP73 was markedly associated with early clinical stage, less lymph node metastasis, absent distant metastasis, squamous cell carcinoma and favorable histological grade. The Kaplan–Meier method and log-rank test were performed based on the expression level of TP73 in a cervical cancer cohort from the TCGA database, and showed that TP73 expression was positively correlated with overall survival time in cervical cancer patients. Moreover, univariate and multivariate Cox proportional hazards regression model indicated that high TP73 expression was identified as an independent factor for predicting favorable overall survival in cervical cancer patients. In conclusion, TP73 expression is increased in cervical cancer tissues and cells, and acts as a credible biomarker for predicting favorable overall survival in cervical cancer patients.

Influence of Biological Parameters Assessed in [18F]FDG PET/CT on Overall Survival in Cervical Cancer Patients.

The aim of this study was to estimate the influence of biological parameters assessed in [F]FDG PET/CT on overall survival (OS) in cervical cancer patients. Retrospective analysis was performed on a group of 371 patients with newly diagnosed and histologically confirmed cervical cancer. PET biological parameters in primary tumor including SUVmax, SUVmean, total lesion glycolysis (TLG), metabolic tumor volume (MTV), heterogeneity, and parameters referring both to primary tumor and metastatic lesions: SUVtotal, TLGtotal, and MTVtotal, were analyzed. Based on PET/CT results, 3 subgroups were identified: cervical only-with disease limited only to the cervix (38%), +regional nodes-where increased glucose accumulation in addition to the cervical area was also observed in regional lymph nodes (36%), and +distal metastases-where PET scan showed a disseminated disease (26%). Depending on the stage of the disease, in the cervical-only group, 5-year survival rate was 86%; in the +regional nodes group, it was 80%; whereas in the +distal metastases group, 5-year survival rate was only 55%. However, based on Cox regression model, significant influence on OS was found only in heterogeneity of primary tumor; more inhomogeneous tumors suggest worse prognosis (0.25 ± 0.04 vs 0.16 ± 0.09, P < 0.001), SUVtotal (76.6 ± 130.1 vs 45.4 ± 73.4, P = 0.002), and MTVtotal (79.03 ± 88.27 vs 63.00 ± 83.80 cm, P = 0.03). For heterogeneity, cutoff point suggesting worse prognosis was 0.18; for SUVtotal, 52.3; and for MTVtotal, 66.55 cm. Stage of disease assessed in [F]FDG PET/CT significantly influences survival rate in patients with cervical cancer. SUVtotal, MTVtotal, and heterogeneity of primary tumor are independent prognostic factors on OS in cervical cancer patients.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis

Background: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. Material and Methods: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. Results: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28–0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03–3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). Conclusions: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Effect of radiotherapy on the survival of cervical cancer patients: An analysis based on SEER database.

Cervical cancer is among the most frequent cancer types in women worldwide. Radiotherapy, including external beam radiation and brachytherapy, is one of the commonly used treatment options for cervical cancer. However, the adverse effects of radiation therapy on cervical cancer survival have been poorly investigated with inconclusive results. Therefore, the aim of this study was to determine the suitable radiotherapy modality according to patients' characteristics. A retrospective survival analysis of 44,602 patients was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate proportional hazard Cox model was used to evaluate the prognostic impact of different radiotherapy modalities, primary surgery, age, TNM stage, and tumor size. Our results indicated that patients without primary surgery, diagnosed at older age (≥45 years' old), at advanced TNM stages (III/IV) or with larger tumor size (≥3 cm) could benefit from radiotherapy. However, radiotherapy was detrimental in patients with primary surgery, diagnosed at younger age (<45 years' old), at earlier TNM stages (I/II) or with smaller tumor size (<3 cm). In addition, external beam radiation was in most cases less effective compared with combined external beam and brachytherapy. These results highlighted the necessity of realizing personalized radiotherapy treatments for patients with cervical cancer.

Identification of candidate biomarkers correlated with the diagnosis and prognosis of cervical cancer via integrated bioinformatics analysis.

Background: Cervical carcinoma is one of the most common malignant gynecological tumors and is associated with high rates of morbidity and mortality. Early diagnosis and early treatment can reduce the mortality rate of cervical cancer. However, there is still no specific biomarkers for the diagnosis and detection of cervical cancer prognosis. Therefore, it is greatly urgent in searching biomarkers correlated with the diagnosis and prognosis of cervical cancer.Results: The mRNA and microRNA expression profile datasets (GSE7803, GSE9750, GSE63514, and GSE30656) were downloaded from the Gene Expression Omnibus database (GEO). The three microarray datasets were integrated to one via integrated bioinformatics. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained by R software. The protein–protein interaction (PPI) networks of the DEGs were performed from the STRING database and further visualized by Cytoscape software. A total of 83 DEGs and 14 DEMs were screened from the microarray expression profile datasets. The miRNAs validated to be associated with cervical cancer were obtained using HMDD online website and the target genes of DEMs were identified using the miRWalk2.0 online database. ESR1, PPP1R3C, NSG1, and TMPRSS11D were the gene targets of hsa-miR-21; the targets of hsa-miR-16 were GYS2, ENDOU, and KLF4. These targets were all downregulated in cervical cancer. Finally, we verified the expression of those targets in cervical tissues from TCGA and GTEx databases and analyzed their relationship with survival of cervical cancer patients. In the end, the expression of key genes in cervical cancer tissues was verified via experiment method, we found KLF4 and ESR1 were downregulated in tumor tissues.Conclusion: This study indicates that KLF4 and ESR1 are downregulated by the upregulated miR21 and miRNA16 in cervical cancer, respectively, using bioinformatics analysis, and the lower expression of KLF4 and ESR1 is closely related to the poor prognosis. They might be of clinical significance for the diagnosis and prognosis of cervical cancer, and provide effective targets for the treatment of cervical cancer.

The effect of uterine involvement on surgical outcomes, recurrence, and survival in cervical cancer patients undergoing radical hysterectomy

The effect of uterine involvement on surgical outcomes, recurrence, and survival in cervical cancer patients undergoing radical hysterectomy

Association of forkhead box protein O1 and paired box gene 3 overexpression with prognosis in patients with cervical cancer.

e14519 Background: Transcriptional factor FOXO1and PAX3 has been reported to play an imported role in human cancer, but the role in cervical cancer has not yet been clarified. Here, we evaluated the functional role of FOXO1 with cervical cancer cells and the expression together with clinical significance of FOXO1 and PAX3 among cervical lesions was investigated. Methods: In vitro assessment of cell functions by cell viably assay, cell migration and invasion assay was evaluated using FOXO1 knockdown cervical cancer cell lines. Immuno-histochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with tissue microarray (TMA) consisting of 209 cervical cancers, 366 high grade cervical intraepithelial neoplasias (CIN), 130 low grade CIN and 328 matched nonadjacent normal cervical epithelial tissues. The clinical significance was investigated by comparing the data with various clinicopathologic characteristics, including survival in cervical cancer. Results: In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability ( p&lt; 0.001), migration ( p&lt; 0.001) and invasion ( p&lt; 0.05) supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p&lt; 0.001) and cancer tissue (both p&lt; 0.001) than in normal tissue. FOXO1 expression showed significant correlation with PAX3 (Spearman’s rho = 0.377, p&lt; 0.001) in a cervical cancer. Multivariate analysis indicates that FOXO1 expression (hazard ratio = 4.01 [95% CI, 1.22–13.10], p= 0.021) and advanced FIGO stage (hazard ratio = 3.89 [95% CI, 1.35–11.19], p= 0.012) were independent prognostic factor on overall survival. Conclusions: This study reveals the association between FOXO1 and PAX3 expression with clinicopathologic variables, including survival of cervical cancer patients. Our results not only suggest the promising potential of FOXO1 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and the pathogenesis of cervical cancer.

Cervical cancer harboring a Rb1 mutation may sensitize to cisplatin via PI3K/AKT pathway by regulating apoptosis.

5531 Background: Cervical cancer is one of the most common malignant tumors in women and major causes of cancer death in women. Although concurrent chemoradiotherapy has improved the treatment of cervical cancer, due to the heterogeneity of the tumor to chemotherapy or radiation therapy, especially the varied response to chemotherapy, the patients respond differently to the same therapeutic regimen, furthermore some patients get rapid progression. Therefore, we attempted to analyze the potential relationship between genomic mutation and chemotherapy response and survival in cervical cancer patients. Methods: Clinical information and sequencing data of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) in Genomic Data Commons (GDC) data portal were obtained through TCGAbiolinks. Only patients with stage IIB-IV CESC who received cisplatin only and were included. Cisplatin sensitivity data and sequencing data of CESC cell lines were obtained from the Genomics of Drug Sensitivity in Cancer (GDSC). Cox regression analysis, Kaplan-Meier survival analysis, differential analysis of gene expression and functional enrichment were used to explore the role of different mutations in survival and cisplatin sensitivity. Results: A total of 48 patients with stage IIB-IV CESC were enrolled. 77 genes with mutation frequency &gt; 10% were included in final analysis . Multivariate analysis showed that the mutation of Rb1 was an independent predictor of overall survival (OS) (HR = 0.07, 95%CI 0.01-0.73, P = 0.026). Patients with mutant Rb1 had better overall survival (134.2 versus 86.8 months) compared with patients with wild-type Rb1. The half maximal inhibitory concentration (IC50) of the mutant Rb1 cell line to cisplatin was significantly lower than that of the wild-type cell line (3.49 versus 10.15μM, P = 0.038). A total of 332 differently expressed genes (DEGs) were identified and the KEGG pathway enrichment analysis showed that most DEGs were enriched in the PI3K/AKT pathway (P = 0.015). Conclusions: We found that Rb1 mutation was an independent survival predictor in stage IIB-IV CESC, and CESC patients with Rb1 mutation may be more sensitive to cisplatin.

Volumetric assessment of apparent diffusion coefficient predicts outcome following chemoradiation for cervical cancer

ObjectiveTo determine the utility of volumetric diffusion weighted imaging (DWI) compared to other clinical factors for predicting recurrence and survival in cervical cancer patients treated with definitive chemoradiation. Methods and materialsWe retrospectively studied cervical cancer patients treated with definitive chemoradiation between 2009–2013 at a single institution with a baseline MRI with DWI and 18F-FDG positron emission tomography/computed tomography (FDG-PET) scan. To identify clinical and imaging metrics correlated with survival and recurrence endpoints, variable importance values were calculated from random forest models. To provide clinically relevant threshold values, recursive partitioning analysis dichotomized patients into potential risk groups based on selected metrics. Cox’s proportional hazard models assessed the effect of clinical and imaging factors on survival endpoints. ResultsNinety-three patients were included in the analysis (median age 50 years). At a median follow-up of 35.6 months, 32 patients (34%) had disease recurrence. In the best multivariate model including clinical and imaging parameters, 90th percentile ADC < 1.917 was the only significantly associated factor with worse progression free survival (PFS). Overall survival, PFS, and distant metastasis free survival (DMFS) were significantly different between patient groups divided on 90th percentile ADC with threshold of 1.917 × 10−3 mm2/s and MRI volume with threshold of 18.9 cc (P = 0.037, P = 0.0002, P = 0.001). High MRI volume and low ADC were associated with worse clinical outcomes. ConclusionsVolumetric 90th percentile ADC value of the primary tumor on pretreatment MRI was a significant predictor of PFS and DMFS in cervical cancer patients, independent of established clinical factors and SUV on FDG-PET.

Epigenetic silencing of Rab39a promotes epithelial to mesenchymal transition of cervical cancer through AKT signaling

The objective of this study was to investigate the functional role of Rab39a in human cervical cancer (CC) and the underlying molecular mechanisms. We first measured Rab39a mRNA expression in CC tissues and paired non-tumor tissues by quantitative real-time PCR (QRT-PCR). Overall survival of CC patients with different mRNA levels of Rab39a in The Cancer Genome Atlas (TCGA) database was assessed by Kaplan-Meier survival curves analysis. Next methylation-specific PCR (MSP) was performed to determine the expression mechanism of Rab39a. Then cell proliferation, migration and invasion of Rab39a-transfected or mock-transfected cervical cancer cells were determined by CCK-8, flow cytometry, wound healing, transwell migration and invasion assays, respectively. Finally, the molecular mechanism by which Rab39a modulated CC cell epithelial-mesenchymal transition (EMT) was explored. It was found that Rab39a mRNA was significantly down-regulated in the high-risk patients compared to the low-risk patients (p = 0.0054). Six of seven cancer tissues with lymph node metastasis express low Rab39a mRNA compared to the surrounding non-tumor tissues. Cervical cancer patients with low level of Rab39a were showed a poorly clinical outcome (p = 0.004). Loss of Rab39a expression in cervical cancer tissues was associated with the aberrant DNA methylation in the promoter of Rab39a gene. Disrupted Rab39a expression in cervical cancer cells could be restored after treatment with the demethylated agent 5-Aza-2'-deoxycytidine. Furthermore, it was found that Rab39a hardly influenced cell growth but significantly suppressed cell migration, invasion and EMT process. Rab39a exerted its potential suppressor functions through inhibiting AKT phosphorylation. The inhibition effects of Rab39a could be blocked by AKT pathway inhibitor. Collectively, our data shows that Rab39a is a potential epigenetic silenced tumor suppressor inhibiting cancer invasion and migration through modulating the AKT signaling.

Survival outcomes of patients with cervical cancer and accompanying hydronephrosis: A systematic review of the literature.

Hydronephrosis is a sign of advanced stage disease in patients with cervical cancer. Its presence is believed to negatively affect the survival of patients. To date, however, consensus in this field is still lacking. The purpose of the present systematic review is to gather the available data and to provide directions for future research in the field. We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRA and Google Scholar databases from inception till June 2018. Overall, 22 studies were included in the present systematic review that evaluated outcomes from 8521 patients with cervical cancer. The findings of our systematic review support that hydronephrosis negatively affects the overall survival of cervical cancer patients. Specifically, the reported 5- year OS hazards ratio for hydronephrosis ranged between 1.34 and 3.74. Outcomes concerning the disease-free survival of these patients were, however, less discrete. None of the included studies reported whether the decreased survival of patients with hydronephrosis was attributed to complications of obstructive uropathy such as uremia and sepsis. Thus, it remains, to date, unclear whether placement of ureteral stents or percutaneous nephrostomy may actually benefit these patients. More studies are needed to evaluate the actual impact of hydronephrosis on survival rates at the various stages of cervical cancer and to help establish consensus regarding the optimal mode of management of these patients.

A low albumin to globulin ratio with a high serum globulin level is a prognostic marker for poor survival in cervical cancer patients treated with radiation based therapy.

We investigated whether the pretreatment albumin to globulin ratio, serum albumin level, and serum globulin level can be used to predict survival among cervical cancer patients treated with radiation based therapy and assessed globulin fractions. We retrospectively enrolled 128 patients with cervical cancer treated with radiation based therapy at our institution between 2010 and 2015. The associations of the pretreatment albumin to globulin ratio, and serum albumin and globulin levels with overall survival were assessed. Additionally, the associations of the globulin fractions with the serum globulin levels and overall survival were evaluated. Median follow-up duration was 30 months (IQR 16-44 months). A low albumin to globulin ratio (< 1.53) was found to be an independent prognostic factor for overall survival (HR= 3.07; 95% CI, 1.03 to 13.3; P=0.044). On evaluating serum globulin and albumin separately, a high serum globulin level was significantly associated with overall survival (cut-off value 2.9 g/dL; HR=3.74; 95% CI 1.08 to 23.6; P=0.036) whereas a low serum albumin level was not associated with overall survival (cut-off value 3.6 g/dL; HR=1.77; 95% CI 0.57 to 4.54; P=0.29). Electrophoresis data of the serum proteins revealed that the γ-globulin fraction was most strongly correlated with the globulin levels (P<0.001). Furthermore, a high γ-globulin level (≥1.28 g/dL) was significantly associated with poor overall survival (log rank test, P=0.034). A pretreatment low albumin to globulin ratio, which might be attributable to a high serum globulin level, can be used to predict poor prognosis in cervical cancer patients treated with radiation based therapy.

LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ

Accumulating evidence suggests that lncRNAs play key roles in many cancers. It has been reported that long non‐coding RNA SNHG14 promotes cell proliferation and metastasis in multiple cancers. However, the role and underlying molecular mechanism of SNHG14 in cervical cancer (CC) remain largely unclear. In this study, we discovered that the relative expression of SNHG14 was significantly upregulated in CC tissues and cells, and associated with the overall survival of CC patients. Moreover, knockdown of SNHG14 significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in CC. Molecular mechanism explorations revealed that SNHG14 acted as a sponge of miR-206 and that YWHAZ was a downstream target gene of miR-206 in CC. Spearman’s correlation analysis uncovered a significantly negative correlation between SNHG14 (or YWHAZ) and miR-206 expression, while a significantly positive correlation between SNHG14 and YWHAZ expression in CC tissues. We also found that the effect of SNHG14 knockdown on the CC progression could be partly rescued by overexpression of YWHAZ at the same time. Our findings revealed that SNHG14 acted as a sponge of miR-206 to regulate the expression of YWHAZ in CC, hinting the promising therapeutic target role of SNHG4 for CC patients.