[To design an intelligent analysis platform for the disabled population data].

OBJECTIVE: To design demand-oriented intelligent analysis platform framework for the disabled population data from overall management to security. METHODS: DATAI-WebEx, active learning, Browser/Server architecture, role-role-based access control, Bayesian network, GIS analysis technology, cluster analysis, regression analysis and other intelligent technologies were used in this study, which provided the functions of multi-source heterogeneous disabled population data fusion, intelligent analysis, secure access and data sharing. RESULTS: The disability data warehouse and intelligent analysis platform can realize the structured and unstructured information disabled population data alignment and data fusion. Also, it can provide disability risk module clustering, disability risk factor identification, disabled distribution analysis, disability scale dynamic trajectory prediction, early warning, disability grade development. Moreover, it can provide a guarantee for the safe and convenient access of sensitive data with the support of "classified boxes", and realize the safe sharing of data of the disabled population. CONCLUSION: The disability data warehouse and intelligent analysis platform can provide the services of "comprehensive fusion-intelligent mining-safe sharing".

Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

BACKGROUND: Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression. METHODS: qRT-PCR and western blot assays were used to detect relevant RNA and protein expressions. In vitro functional assays, including CCK8, EdU, TUNEL and transwell assays were applied to explore the functions of CTBP1-AS2 in CC cell proliferation, apoptosis and migration. In vivo animal study was utilized to investigate the role of CTBP1-AS2 in tumor growth. Luciferase reporter, RNA pull down and RIP assays were performed to determine the specific mechanical relationship between CTBP1-AS2, miR-3163 and ZNF217. RESULTS: CTBP1-AS2 was significantly overexpressed in CC cell lines. Knockdown of CTBP1-AS2 curbed cell proliferation, migration and invasion, while stimulated cell apoptosis in vitro. CTBP1-AS2 facilitated xenograft tumor growth in vivo. Cytoplasmic CTBP1-AS2 was found to be a miR-3163 sponge in CC cells. MiR-3163 inhibition abolished the anti-tumor effects of CTBP1-AS2 knockdown. Additionally, Zinc finger protein 217 (ZNF217) was identified as a direct target of miR-3163. CTBP1-AS2 acted as a miR-3163 sponge to elevate ZNF217 expression. ZNF217 up-regulation abrogated the tumor suppressing effects of CTBP1-AS2 knockdown. CONCLUSION: CTBP1-AS2 regulates CC progression via sponging miR-3163 to up-regulate ZNF217.

Identification of lysine acetylome in cervical cancer by label-free quantitative proteomics.

BACKGROUND: Lysine acetylation is a post-translational modification that regulates a diversity of biological processes, including cancer development. METHODS: Here, we performed the quantitative acetylproteomic analysis of three primary cervical cancer tissues and corresponding adjacent normal tissues by using the label-free proteomics approach. RESULTS: We identified a total of 928 lysine acetylation sites from 1547 proteins, in which 495 lysine acetylation sites corresponding to 296 proteins were quantified. Further, 41 differentially expressed lysine acetylation sites corresponding to 30 proteins were obtained in cervical cancer tissues compared with adjacent normal tissues (Fold change > 2 and P < 0.05), of which 1 was downregulated, 40 were upregulated. Moreover, 75 lysine acetylation sites corresponding to 58 proteins were specifically detected in cancer tissues or normal adjacent tissues. Motif-X analysis showed that kxxxkxxxk, GkL, AxxEk, kLxE, and kkxxxk are the most enriched motifs with over four-fold increases when compared with the background matches. KEGG analysis showed that proteins identified from differently and specifically expressed peptides may influence key pathways, such as Notch signaling pathway, viral carcinogenesis, RNA transport, and Jak-STAT, which play an important role in tumor progression. Furthermore, the acetylated levels of CREBBP and S100A9 in cervical cancer tissues were confirmed by immunoprecipitation (IP) and Western blot analysis. CONCLUSIONS: Taken together, our data provide novel insights into the role of protein lysine acetylation in cervical carcinogenesis.

Integrated analysis of immune-related genes in endometrial carcinoma.

BACKGROUND: Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis. METHODS: Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results. RESULTS: A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan-Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells. CONCLUSIONS: Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.

Effect of hyperoside on cervical cancer cells and transcriptome analysis of differentially expressed genes.

BACKGROUND: Hyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes. METHODS: Cervical cancer HeLa and C-33A cells were cultured and the effect of Hy treatment was determined using the Cell Counting Kit-8 (CCK-8) assay. After calculating the IC50 of Hy in HeLa and C-33A cells, the more sensitive to Hy treatment cell type was selected for RNA-Seq. Differentially expressed genes (DEGs) were identified by comparing gene expression between the Hy and control groups. Candidate genes were determined through DEG analysis, protein interaction network (PPI) construction, PPI module analysis, transcription factor (TF) prediction, TF-target network construction, and survival analysis. Finally, the key candidate genes were verified by RT-qPCR and western blot. RESULTS: Hy inhibited HeLa and C33A cell proliferation in a dose- and time-dependent manner, as determined by the CCK-8 assay. Treatment of C-33A cells with 2 mM Hy was selected for the subsequent experiments. Compared with the control group, 754 upregulated and 509 downregulated genes were identified after RNA-Seq. After functional enrichment, 74 gene ontology biological processes and 43 Kyoto Encyclopedia of Genes and Genomes pathways were obtained. According to the protein interaction network (PPI), PPI module analysis, TF-target network construction, and survival analysis, the key genes MYC, CNKN1A, PAX2, TFRC, ACOX2, UNC5B, APBA1, PRKACA, PEAR1, COL12A1, CACNA1G, PEAR1, and CCNA2 were detected. RT-qPCR was performed on the key genes, and Western blot was used to verify C-MYC and TFRC. C-MYC and TFRC expressions were lower and higher than the corresponding values in the control group, respectively, in accordance with the results from the RNA-Seq analysis. CONCLUSION: Hy inhibited HeLa and C-33A cell proliferation through C-MYC gene expression reduction in C-33A cells and TFRC regulation. The results of the current study provide a theoretical basis for Hy treatment of cervical cancer.

Identification of Subpathway Signatures For Ovarian Cancer Prognosis by Integrated Analyses of High-Throughput miRNA and mRNA Expression.

BACKGROUND/AIMS: Ovarian cancer (OC) causes more death and serious conditions than any other female reproductive cancers, and many expression signatures have been identified for OC prognoses. However, no significant overlap is found among signatures from different studies, indicating the necessity of signature identifications at the functional level. METHODS: We performed an integrated analyses of miRNA and gene expressions to identify OC prognostic subpathways (pathway regions). Using The Cancer Genome Atlas data set, we identified core prognostic subpathways, and calculated subpathway risk scores using both miRNA and gene components. Finally, we performed global risk impact analyses to optimize core subpathways using the random walk algorithm. RESULTS: Subpathway-level analyses displayed more robust results than the gene- and miRNA-level analyses. Moreover, we verified the advantage of core subpathways over the entire pathway-based results and their prognostic performance in two independent validation data sets. Based on the global impact score, 13 subpathway signatures were selected and a combined subpathway-based risk score was further calculated for OC patient prognoses. CONCLUSIONS: Overall, it was possible to systematically perform integrated analyses of the expression levels of miRNAs and genes to identify prognostic subpathways and infer subpathway risk scores for use in OC clinical applications.

Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer.

AIMS: As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer and to evaluate its clinical significance. METHODS AND RESULTS: The mRNA and protein expression levels of EIF5A2 were analysed in 20 tissue samples of FIGO stage I-II cervical cancer and paired surrounding non-tumour cervical tissues by real-time polymerase chain reaction and western blot analysis. Immunohistochemistry was performed to examine EIF5A2 protein expression in paraffin-embedded tissues from 314 patients with cervical cancer. The mRNA and protein expression levels of EIF5A2 were significantly elevated in tumour tissues. The increased EIF5A2 expression was correlated with higher FIGO stage (P < 0.001), deep cervical stromal invasion (P = 0.026), lymphovascular space involvement (P = 0.002), pelvic lymph node metastasis (P < 0.001) and postoperative recurrence (P < 0.001) in patients with cervical cancer. Patients with tumours showing high EIF5A2 expression had a poorer survival time than those with normal EIF5A2 expression, especially the patients with negative pelvic lymph nodes and FIGO stage II. In addition, multivariate Cox analysis showed that high EIF5A2 expression was an independent prognostic factor for overall survival [hazard ratio 1.949; 95% confidence interval (CI) 1.116-3.404; P = 0.019] and disease-free survival (hazard ratio 1.980; 95% CI 1.189-3.297; P = 0.009). CONCLUSIONS: EIF5A2 overexpression may contribute to cancer progression and poor prognosis. Therefore, EIF5A2 could be a novel potential prognostic marker for FIGO stage I-II cervical cancer.

DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer.

Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.

Overexpression of Siah2 Is Associated With Poor Prognosis in Patients With Epithelial Ovarian Carcinoma.

OBJECTIVES: Seven in absentia homolog 2 (Siah2) is an E3 ubiquitin ligase that is expressed in mammals and is homologous to seven in absentia in Drosophila. Siah2 is involved in the progression of many malignancies. However, the role of Siah2 in ovarian cancer remains unclear. This study aims to evaluate the prognostic value of Siah2 expression for epithelial ovarian carcinoma (EOC) patients. MATERIALS AND METHODS: Immunohistochemical analysis was conducted using 32 normal ovarian specimens and 122 ovarian carcinoma specimens, respectively. We analyzed the correlations of Siah2 expression with the clinicopathological factors and prognosis of ovarian cancer patients. χ Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were conducted for statistical analyses. RESULTS: Immunohistochemical staining demonstrated that the expression of Siah2 was higher in the EOC tissues than in the normal tissues. High Siah2 expression positively correlated with histological grade and lymph node metastasis but not with age, histologic type, International Federation of Gynecology and Obstetrics staging, and CA125. Patients with positive Siah2 expression showed lower overall survival and disease-free survival rates than those with negative Siah2 expression (P < 0.05 for both). Multivariate Cox analysis indicated that Siah2 was an independent parameter for overall survival (hazards ratio, 2.166; 95% confidence interval, 1.182-3.970; P = 0.012) and disease-free survival (hazards ratio, 1.819; 95% confidence interval, 1.030-3.216; P = 0.039). CONCLUSIONS: Siah2 is possibly involved in tumor development and progression in EOC. Thus, Siah2 is a promising biomarker for predicting the prognosis of ovarian cancer patients and may serve as a novel target for treating ovarian carcinoma.

Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis.

This study aimed to explore the clinical significance of AAA+ (ATPases associated with various cellular activities) nuclear coregulator cancer-associated (ANCCA) protein expression in endometrial carcinoma (EC). Correlations of ANCCA expression with clinicopathological factors and prognosis of EC patients were analyzed. Expression of ANCCA was detected in EC from 207 patients along with corresponding normal endometrium specimens by immunohistochemistry. ANCCA immunoreactivity was overexpressed in EC cases compared with that in normal endometrium (P < 0.001). High ANCCA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence but not with age and histological type. Patients with high ANCCA expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low ANCCA expression (P = 0.001 and 0.002, respectively). Cox multivariate analysis showed that high ANCCA expression was an independent prognostic factor for both OS (hazard ratio (HR) = 4.954, 95 % confidence interval (CI) = 1.537-15.966; P = 0.007) and DFS of patients with EC (HR = 4.237, 95 % CI = 1.295-13.859; P = 0.017). We identified ANCCA protein expression as a novel independent poor prognostic indicator in EC.

Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis.

OBJECTIVE: Special AT-rich sequence-binding protein 1 is aberrantly expressed in various malignant tumors. However, the expression and function of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma have not been reported. The objective of this study was to investigate the clinical significance of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma. METHODS: In this study, we investigated the expression of special AT-rich sequence-binding protein 1 through immunohistochemistry in 25 normal cervix specimens and 167 cervical squamous cell carcinomas and analyzed its association with various clinicopathologic parameters, including patient outcome. RESULTS: Special AT-rich sequence-binding protein 1 protein was detected in 58 (34.7%) out of 167 patients and was highly related to International Federation of Gynecology and Obstetrics stage, histologic grade, lymph node metastasis, vascular-lymphatic invasion and recurrence of cervical squamous cell carcinoma. Patients with positive special AT-rich sequence-binding protein 1 expression had significantly lower overall survival and disease-free survival compared with patients with negative expression of special AT-rich sequence-binding protein 1 (P = 0.001 and P < 0.001, respectively). A multivariate Cox regression analysis revealed that special AT-rich sequence-binding protein 1 was an independent prognostic marker for both disease-free survival and overall survival of cervical squamous cell carcinoma patients (P = 0.038 and P = 0.010, respectively). A multivariate logistic regression analysis showed that special AT-rich sequence-binding protein 1 expression was strongly associated with lymph node metastasis (odds ratio = 2.497; P = 0.032). Sensitivity and specificity of special AT-rich sequence-binding protein 1 for lymph node metastasis were 61.0 and 73.8%, respectively. CONCLUSIONS: These results showed that special AT-rich sequence-binding protein 1 expression was associated with tumor progression, metastasis and poor prognosis in cervical squamous cell carcinoma. It may serve as a new prognostic biomarker or a target for improving the treatment efficiency of patients with cervical squamous cell carcinoma.

Overexpression of special AT-rich sequence-binding protein 1 in endometrial cancer: a clinicopathologic study.

OBJECTIVE: Special AT-rich sequence-binding protein 1 (SATB1), as a genome organizer, serves important functions in tumor progression and metastasis. The SATB1 is overexpressed in various malignant tumors. However, the expression and prognostic value of SATB1 in endometrial cancer remain unknown. The aim of this study was to explore the prognostic values of SATB1 expression in endometrial cancer. METHODS/MATERIALS: We investigated the expression of SATB1 in 172 untreated endometrial cancer tissues and 25 normal endometrial tissues through immunohistochemical staining. We also analyzed the association of SATB1 level with clinicopathologic parameters and determined its prognostic significance. RESULT: Special AT-rich sequence-binding protein 1 was expressed in 78 (45.3%) of the 172 endometrial cancer samples, but not in the normal endometrial samples. The positive expression of SATB1 was associated with clinicopathologic factors, such as International Federation of Gynecology and Obstetrics stage, histological grade, myometrial invasion depth, lymph node metastasis, vascular/lymphatic invasion, and recurrence. The patients with positive SATB1 expression had worse overall survival and disease-free survival rates than the patients with negative SATB1 expression (P < 0.001 for both). Multivariate Cox analysis indicated that SATB1 was an independent parameter for overall survival (hazards ratio, 2.928; 95% confidence interval, 1.072-7.994; P = 0.036) and disease-free survival (hazards ratio, 2.825; 95% confidence interval, 1.111-7.181; P = 0.029). CONCLUSIONS: Results showed that SATB1 may be involved in tumor development and progression in endometrial cancer, may serve as a promising biomarker for predicting the prognosis of endometrial cancer patients, and thus may act as a novel target for treating endometrial carcinoma.

Overexpression of Lysine-Specific Demethylase 1 Is Associated With Tumor Progression and Unfavorable Prognosis in Chinese Patients With Endometrioid Endometrial Adenocarcinoma.

OBJECTIVE: Lysine-specific demethylase 1 (LSD1) is a kind of flavin adenine dinucleotide-dependent amine oxidase that regulates normal cellular differentiation, gene activation, tumorigenesis, and progression. This study aims to detect the expression level of LSD1 in endometrial cancer and to explore its role in the progression and prognosis of endometrioid endometrial adenocarcinoma (EEA). METHODS: Immunohistochemistry was used to examine the expression of LSD1 in 206 EEA specimens, 50 benign endometrial lesion specimens, and 45 normal endometrium specimens. χ Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were applied for the statistical analysis. RESULTS: Compared with normal endometrium and benign endometrial lesion (both P < 0.001), LSD1 was overexpressed in EEA. LSD1 expression was correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, vascular/lymphatic invasion, depth of myometrial invasion, and lymph node metastasis. Results of the Kaplan-Meier analysis indicated that LSD1 expression was associated with overall survival (OS) and disease-free survival (DFS) of EEA. The negative expression LSD1 group had longer OS and DFS than did the positive expression group. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that the LSD1 expression status was an independent prognostic factor for both OS (P = 0.027) and DFS (P = 0.016) of patients with EEA. CONCLUSIONS: Overexpression of LSD1 may contribute to the progression of EEA and may thus serve as a new biomarker to predict the prognosis of EEA.

Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer.

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P<0.001), higher histologic grade (P=0.017), deep myometrial invasion (P=0.030), lymphovascular space invasion (P=0.011), lymph node metastasis (P<0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P<0.001 for both) and Ki-67 (P=0.007 and P=0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P>0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P=0.029) and lymph node metastasis (P=0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.

Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer prognosis and therapeutics.

Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor progression and oncogenesis. The aim of this study was to investigate the role of USP22 and the association with its potential targets in patients with cervical cancer. To our knowledge, this is the first study that determines the relationship between USP22 expression and clinicopathological significance in cervical cancer. The immunohistochemistry results showed that USP22 protein was overexpressed in cervical cancer samples compared with normal cervical tissues (P < 0.001). Moreover, clinicopathological analysis showed that USP22 expression was highly related to International Federation of Gynecology and Obstetrics stage, Ki67, lymph node metastasis, and histology grade. The results of Kaplan-Meier analysis indicated that patients with high USP22 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients with low expression of USP22 (P < 0.001). Multivariate Cox regression analysis revealed that USP22 expression status was an independent prognostic marker for both OS and DFS of patients with cervical cancer. It is suggested that USP22 overexpression may be associated with poor prognosis in cervical cancer. It may represent a novel prognostic biomarker or a target for improving the treatment efficiency of patients with cervical cancer.

Preoperative neutrophil-lymphocyte ratio before platelet-lymphocyte ratio predicts clinical outcome in patients with cervical cancer treated with initial radical surgery.

OBJECTIVE: Several inflammatory parameters are applied to predict the survival of patients with various cancers. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are 2 nonspecific markers of systemic inflammation. This study aimed to evaluate the clinicopathologic and prognostic values of NLR and PLR in patients with cervical cancer undergoing primary radical hysterectomy with pelvic lymphadenectomy. METHODS: A total of 460 cervical cancer patients were enrolled in this study. These patients were histologically confirmed with cervical cancer from February 2005 to June 2008, at the Department of Gynecology, the Third Affiliated Hospital of Harbin Medical University, China. Their clinical and histopathological markers and complete blood counts were collected and analyzed. Prognostic factors were assessed by univariate and multivariate analyses. RESULTS: The median NLR and PLR were 2.213 and 150.9, respectively. The clinicopathologic analysis showed that NLR was highly associated with depth of stromal infiltration (P = 0.007) and lymph node metastasis (P = 0.003), and PLR was significantly related to tumor size (P = 0.020) and lymph node metastasis (P = 0.027).Univariate analysis identified high NLR as a statistically significant poor predictive factor for the progression-free survival (PFS) (P = 0.008) and overall survival (OS) (P = 0.014), and PLR exhibited no significance on PFS (P = 0.075) and OS (P = 0.110).Multivariable analysis showed that the NLR was an independent prognostic marker for PFS (hazard ratio, 1.799; 95% confidence interval, 1.069-3.028; P = 0.027), but not for OS (hazard ratio, 1.631; 95% confidence interval, 0.968-2.750; P = 0.066). CONCLUSIONS: Preoperative NLR and PLR were found to be correlated to unfavorable histopathologic features of cervical cancer. The preoperative NLR, but not PLR, may be used as a potential and easy biomarker for survival prognosis in patients with cervical cancer receiving initial radical hysterectomy with pelvic lymphadenectomy.

Roles of PPAR activation in cancer therapeutic resistance: Implications for combination therapy and drug development.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer. In this review, we provided an overview of the roles of excessively activated PPARs in promoting resistance to modern anti-cancer treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The mechanisms through which activated PPARs contribute to therapeutic resistance in most cases include metabolic reprogramming, anti-oxidant defense, anti-apoptosis signaling, proliferation-promoting pathways, and induction of an immunosuppressive tumor microenvironment. In addition, we discussed the mechanisms through which activated PPARs lead to multidrug resistance in cancer, including drug efflux, epithelial-to-mesenchymal transition, and acquisition and maintenance of the cancer stem cell phenotype. Preliminary studies investigating the effect of combination therapies with PPAR antagonists have suggested the potential of these antagonists in reversing resistance and facilitating sustained cancer management. These findings will provide a valuable reference for further research on and clinical translation of PPAR-targeting treatment strategies.

Overexpression of multiple myeloma SET domain (MMSET) is associated with advanced tumor aggressiveness and poor prognosis in serous ovarian carcinoma.

Multiple myeloma SET domain (MMSET) has been shown to be overexpressed in many different cancer tissues. Our study was to investigate the expression of MMSET in serous ovarian carcinoma and to evaluate its clinical significance in patients with serous ovarian carcinoma. Immunohistochemistry was performed to determine the expression of MMSET in 132 serous ovarian carcinoma, 32 normal ovarian and fallopian tube specimens. The high expression of MMSET was observed in 49.2% (65/132) in patients with serous ovarian carcinoma. MMSET high expression correlated with the advanced extent of serous ovarian carcinoma and poor outcome. MMSET may serve as a new molecular marker to predict the prognosis of serous ovarian carcinoma in the clinic.

Clinical significance of yes-associated protein overexpression in cervical carcinoma: the differential effects based on histotypes.

OBJECTIVES: The objective of this study was to explore the prognostic values of Yes-associated protein (YAP) expression in cervical carcinoma. METHODS: We compared the YAP expression of 120 samples from squamous cell carcinomas (SCCs) and 42 samples from adenocarcinomas with 22 normal cervical specimens by immunohistochemistry. The expressions of cytoplasmic and nuclear YAP were analyzed separately. RESULT: Yes-associated protein expression in tumors is significantly higher than the level in normal tissues. In SCCs, cytoplasmic YAP expression is associated with histologic grading, lymph node metastasis, and recurrence. Nuclear expression of YAP is absent in SCC. In adenocarcinomas, cytoplasmic YAP overexpression is associated with histologic grading, and nuclear overexpression is associated with shorter overall survival and disease-free survival. CONCLUSIONS: Our results indicate the oncogenic potential of YAP in cervical cancer and its distinct functions in SCC and adenocarcinoma.

Overexpression of Wnt7a is associated with tumor progression and unfavorable prognosis in endometrial cancer.

BACKGROUND: Wnt7a is a secreted glycoprotein that regulates normal cellular proliferation and differentiation, as well as tumorigenesis and progression. The aim of the present study was to detect the level of expression of Wnt7a in endometrial cancer and explore its role in progression and prognosis of endometrial cancer. METHODS: Immunohistochemistry was used to examine the expression of Wnt7a in 244 endometrial cancer specimens, in 48 benign endometrial lesion specimens, and 43 normal endometrium specimens. χ(2) Analysis, Kaplan-Meier analysis and log-rank test, and multivariate Cox proportional hazards analysis were applied for statistical analysis. RESULTS: Wnt7a was overexpressed in endometrial cancer compared with normal endometrium and benign endometrial lesion (both P < 0.001). Wnt7a expression was correlated with histological grade, International Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, vascular/lymphatic invasion, and lymph node metastasis. The results of Kaplan-Meier analysis indicated that Wnt7a expression was associated with overall survival (OS) and disease-free survival (DFS) of endometrial cancer. The survival of negative expression Wnt7a group had longer OS and DFS compared with the group with positive expression. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that Wnt7a expression status was an independent prognostic factor for both OS and DFS (P = 0.034 and P = 0.009, respectively) of patients with endometrial cancer. CONCLUSIONS: Overexpression of Wnt7a may contribute to the progression of endometrial cancer and thus may serve as a new biomarker to predict the prognosis of endometrial cancer.