Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

The indication and treatment outcome predictors of mifepristone treating ectopic pregnancy.

OBJECTIVE: Ectopic pregnancy is a life-threatening disease and is an important cause of pregnancy-related mortality. MTX is the primary conservative treatment medicine of ectopic pregnancy, and mifepristone is also a promising medicine. Through studying the ectopic cases at the third affiliated hospital of Sun Yat-Sen University, the study aims to analyze the indication and treatment outcome predictors of mifepristone. METHODS: The data of 269 ectopic pregnancy cases treated with mifepristone during the year 2011-2019 were retrospectively collected. Logistic-regression analysis was used to analyze the factors affiliated with the treatment outcome of mifepristone. Then ROC curve was used to analyze the indication and predictors. RESULTS: Through logistic-regression analysis, HCG is the only factor related to the treatment outcome of mifepristone. The AUC of ROC curve predicting treatment outcome with pre-treatment HCG is 0.715, and the cutoff value of ROC curve is 372.66 (sensitivity 0.752, specificity 0.619). The AUC of 0/4 ratio predicting the treatment outcome is 0.886, and the cutoff value is 0.3283 (sensitivity 0.967, specificity 0.683). The AUC of 0/7 ratio is 0.947, and the cutoff value is 0.3609 (sensitivity 1, specificity 0.828). CONCLUSIONS: Mifepristone can be used to treat ectopic pregnancy. HCG is the only factor related to the treatment outcome of mifepristone. Patients with HCG less than 372.66 U/L can be treated by mifepristone. If HCG descends more than 67.18% on the 4th day or 63.91% on the 7th day, it is more likely to have a successful treatment outcome. It is more precise to retest on the 7th day.

The trend of the distribution of ectopic pregnancy sites and the clinical characteristics of caesarean scar pregnancy.

BACKGROUND: Ectopic pregnancy is a life-threatening occurrence and is an important cause of pregnancy-related mortality. We launched the study to investigate the distribution and its variation trend of the ectopic pregnancy sites and the clinical characteristics of caesarean scar pregnancy, to provide information for further clinical practice. METHODS: A total of 3915 patients were included in our study to calculate the distribution of the implantation sites of ectopic pregnancies. Then, we performed a χ2 test for trend and calculated the quantity of each type of ectopic pregnancy during 2012-2015 and 2016-2019 to analyse the variation trend. RESULTS: (1) The proportion of each site of ectopic pregnancy was as follows: tubal pregnancy (84.70%), ovarian pregnancy (1.56%), caesarean scar pregnancy (8.63%), abdominal pregnancy (0.61%), cornual pregnancy (2.68%), cervical pregnancy (0.49%), heterotopic pregnancy (0.43%). (2) Through the χ2 test for trend, the ratio of caesarean scar pregnancy to ectopic pregnancy showed an upward trend (P = 0.005). From 2012 to 2015 and 2016-2019, the ratio of caesarean scar pregnancy to ectopic pregnancy increased from 5.74 to 11.81% (P < 0.001). (3) A total of 72.78% (246/338) caesarean scar pregnancy patients had one caesarean delivery, 25.15% (85/338) had two caesarean deliveries, and 2.07% (7/338) had three caesarean deliveries. A total of 80.18% (271/338) had aborted before. The most common clinical manifestations were amenorrhea (98.52%), abdominal pain (25.74%) and vaginal bleeding (67.76%), the most common sign was uterine enlargement (46.75%). CONCLUSION: As the ratio of caesarean scar pregnancy increases, the caesarean delivery rate should be decreased to decrease the morbidity of caesarean scar pregnancy.

Ectopic pregnancy occurs when a fertilized ovum implants outside the endometrium of the uterine cavity, which is a life-threatening occurrence and is an important cause of pregnancy-related mortality. With the increase in pelvic and intrauterine operations, the distribution of ectopic sites has been changing, but the variation has been insufficiently studied. To investigate the distribution of ectopic sites and its variation trend in depth, we collected the data of 3915 ectopic pregnancy cases from the third affiliated hospital of Sun Yat-Sen University.Through χ² test for trend, the ratio of caesarean scar pregnancy to ectopic pregnancy showed an upward trend (P = 0.005). From 2012 to 2015 and 2016­2019, the ratio of caesarean scar pregnancy to ectopic pregnancy increased from 5.74 to 11.81% (P < 0.001). As the increasing of the ratio of caesarean scar pregnancy to ectopic pregnancy, the clinical characteristics of caesarean scar pregnancy was analysed.A total of 72.78% (246/338) caesarean scar pregnancy patients had one caesarean delivery, 25.15% (85/338) had two caesarean deliveries, and 2.07% (7/338) had three caesarean deliveries. A total of 80.18% (271/338) had aborted before. The most common clinical manifestations were amenorrhea (98.52%), abdominal pain (25.74%) and vaginal bleeding (67.76%), the most common sign was uterine enlargement (46.75%).As the ratio of caesarean scar pregnancy increases, the caesarean delivery rate should be decreased to decrease the morbidity of caesarean scar pregnancy.

Construction and Validation of Nomograms for Predicting the Prognosis of Uterine Leiomyosarcoma: A Population-Based Study.

BACKGROUND Uterine leiomyosarcoma (uLMS) is a rare female malignancy with poor survival rates. The objective of this study was to construct prognostic nomograms for predicting the prognosis of women with uLMS. MATERIAL AND METHODS Patients with uLMS diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The essential clinical predictors were identified via univariate and multivariate Cox analysis models. Nomograms were constructed to predict the 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) rates. Concordance index (C-index) and calibration plots were constructed to validate the predictive performance of nomograms. RESULTS We enrolled 1448 patients with uLMS from the SEER database, with 1016 categorized into a training set and 432 categorized into a validation set. In multivariate analysis of the training set, predictors including age, disease stage, histological grade, tumor size, and surgery type were found to be associated with OS and CSS. Race and chemotherapy were only associated with OS. Construction of nomograms based on these predictors was performed to evaluate the prognosis of uLMS patients. The C-index and calibration curves also showed the satisfactory performance of these nomograms for prediction of prognosis. CONCLUSIONS The developed nomograms are useful tools for precisely analyzing the prognosis of uLMS patients, which could help clinicians in making personalized survival predictions and assessing individualized clinical options.

[Value of hysteroscopy and dilatation and curettage in diagnosis of endometrial cancer].

OBJECTIVE: To evaluated the value of hysteroscopy and dilatation and curettage (DC) in diagnosis of endometrial cancer. METHODS: This retrospective analysis included clinical pathologic data of 3 676 patients with endometrial cancer from Jan. 1, 2000 to Dec. 31, 2010 in hospitals of endometrial cancer prevention projects in Guangdong Province. RESULTS: A total of 3 676 patients with endometrial cancer were divided into DC group (3 211 patients) and hysteroscopy group (465 patients). Compared to the results of pathological diagnosis, the accuracy rate between DC group and in hysteroscopy group were no statistically difference was 91.00% (2 922/3 211) vs 90.75% (422/465; χ² = 0.030, P = 0.862). The accuracy rate, sensitivity, specificity, positive predictive value and negative predictive value of cervical involvement between DC group and hysteroscopy group were 81.28% vs 86.45% (P < 0.01), 24.78% vs 23.68% (P > 0.05), 93.76% vs 98.71% (P < 0.01), 46.75% vs 78.26% (P < 0.01) and 84.95% vs 86.88% (P > 0.05), respectively. Rate of positive peritoneal cytology in DC group was 4.76% (153/3 211), and the rate was 3.23% (15/465) in hysteroscopy group, which were no statistically difference (χ² = 2.206, P = 0.137). There were no statistically difference in 5-year overall survival (91.02% vs 92.03%; χ² = 0.033, P = 0.856) and 5-year progression-free survival (89.81% vs 91.83%; χ² = 1.508, P = 0.219) between DC group and hysteroscopy group. CONCLUSIONS: Hysteroscopy and dilatation and curettage is an effective method in diagnosis of endometrial cancer, especially hysteroscopy is better in diagnosis of cervical involvement. Hysteroscopy don't improve risks of positive peritoneal cytology and don't affect the prognosis of patients with endometrial cancer.

Insulin and hypertonic glucose in the management of aseptic fat liquefaction of post-surgical incision: a meta-analysis and systematic review.

A meta-analysis and systematic review assessing randomised controlled trials (RCTs) was sought to determine whether subcutaneous injection of insulin with hypertonic glucose promotes healing in postoperative incisions with aseptic fat liquefaction. We searched the Cochrane library, Pubmed, EMBASE, National Science Digital Library (NSDL) and China Biological Medicine Database (CBMdisc) for literature published from 1 January 1990 to 30 September 2011. RCTs that evaluated subcutaneous injection of insulin with hypertonic glucose as a treatment for postoperative wound with fat liquefaction were sought. Wound healing was the primary endpoint. Jadad score and Cochrane Collaboration's tool were used for assessing quality of studies and risk of bias. We abstracted data regarding time to wound healing, cost and adverse effects. The random-effects inverse variance model was used for all analyses using weighted mean difference and 95% confidence interval. Eight trials (414 participants) were identified that met the inclusion criteria. Subcutaneous injection of insulin with hypertonic glucose significantly reduces time to healing by 6·33 days compared with conventional drainage, with less cost. There was no report concerning adverse effects. Subcutaneous injection of insulin with hypertonic glucose may improve the healing process in postoperative wounds with aseptic fat liquefaction.

Primary Anterior Medistinal Choriocarcinoma in Male with Lung Metastasis and Pituitary Microadenoma: A Case Report.

The authors report a case of a 29-year-old male presented with bilateral breast enlargement with no significant past medical history or estrogen exposure. Serum ß-human chorionic gonadotropin (HCG) was 14,306.60 mIU and positron emission tomography-computed tomography discovered a malignant mass on the right side of anterior superior mediastinum. Magnetic resonance imaging demonstrated pituitary microadenoma. Pathological biopsy showed poorly differential pituitary adenoma and immunohistochemical staining displayed that CK(+), PLAP(-), AFP(-), HCG(+), CD30(-), Oct3/4(-), CK7(+), TTF-1(-), CD117(-), Ki 67(80+), CK5/6(-), EMA(partial+), inhibin(partial+). A diagnosis of primary anterior mediastinal choriocarcinoma metastasis to bilateral lungs accompanied with pituitary microadenoma was confirmed. Then the patient received chemotherapy combined with immunotherapy. But serum ß-HCG level was still above the normal, and unfortunately, the patient died 6 months after his diagnosis. This case inspires us to think of the possibility of choriocarcinoma when a man presents gynecomastia or lung metastatic symptoms, adding Opdivo to the chemotherapy might not improve the poor treatment outcomes.

EGFR- and AKT-mediated reduction in PTEN expression contributes to tyrphostin resistance and is reversed by mTOR inhibition in endometrial cancer cells.

Loss or mutation of the PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene is associated with resistance to epidermal growth factor receptor (EGFR) inhibitors. However, the mechanism underlying remains elusive. In this study, we aimed to explore whether sensitivity to the EGFR tyrosine kinase inhibitor (TKI) is affected by PTEN status in endometrial cancer cells. PTEN siRNA and the PTEN gene were transfected into HEC-1A and Ishikawa endometrial cancer cells using lentiviral vectors. Cells were treated under various concentrations of RG14620 and rapamycin, which are EGFR and mammalian target of rapamycin (mTOR) inhibitors, respectively. The IC(50) of RG16420 was determined by using the MTT method. Cell apoptosis and the cell cycle were studied, and activation of EGFR, AKT, and p70S6 were detected by Western blot analysis. Loss of PTEN promoted cell proliferation and led to significant increases in the levels of EGFR, phospho-EGFR, AKT, phospho-AKT, and phospho-mTOR proteins. Ishikawa and HEC-1A(PTENkd) cells that displayed loss and inactivation of PTEN function were resistant to RG14620. HEC-1A and Ishikawa(PTEN) cells with intact PTEN were sensitive to RG14620. The combination of two inhibitors was more effective than both monotherapies, particularly in carcinoma cells with PTEN dysfunction. Decreased phospho-EGFR protein expression was observed in all cell lines that were sensitive to RG14620. Decreased phospho-AKT and phospho-p70S6 protein expression was observed in PTEN-intact cells that were sensitive to RG14620. PTEN loss results in resistance to EGFR TKI, which was reversed by PTEN reintroduction or mTOR inhibitor treatment. The combined treatment of EGFR TKI and the mTOR inhibitor provided a synergistic effect by promoting cell death in PTEN-deficient and PTEN-intact endometrial cancer cells, particularly in PTEN-deficient carcinoma cells with up-regulated EGFR activation.

An Acid Response IR780-Based Targeted Nanoparticle for Intraoperative Near-Infrared Fluorescence Imaging of Ovarian Cancer.

Introduction: Complete resection of all visible disease (R0 resection) is critical for the treatment of ovarian cancer patients, and accurate real-time guidance provided by intraoperative near-infrared (NIR) fluorescence images is beneficial for achieving complete resection of all visible disease. Methods: Based on the optical properties of IR780 and the characteristics of the acidic tumor microenvironment, we develop a new smart nanoparticle (eg, FA-IR780&PFOB-SNPs) by using the pH response nano framework (FA-PEG-PLGA-PEOz) and adjusting the amount of IR780. The FA-IR780&PFOB-SNPs was characterized for morphology, microstructure, particle size, pH-response, drug-loading efficiency and biological safety. The ultraclear fluorescence Navigation Endoscopy System was applied to evaluate the tumor recognition of FA-IR780&PFOB-SNPs in vivo. Results: The structure of FA-IR780&PFOB-SNPs was stable in a neutral environment, and the near-infrared (NIR) fluorescence was turned off, while the structure of FA-IR780&PFOB-SNPs was degraded in the acidic tumour microenvironment, and the NIR fluorescence was turned on. Through the ovarian subcutaneous xenograft tumour and ovarian intraperitoneal xenograft tumour models, it was confirmed that FA-IR780&PFOB-SNPs could clearly display the boundaries of abdominal micron-sized tumours through near-infrared fluorescence imaging, with a TBR greater than 5. Conclusion: The FA-IR780&PFOB-SNPs have the potential to provide to ovarian cancer intraoperative near infrared fluorescence navigation during precision tumour resection to achieve R0 and improve the prognosis of ovarian cancer patients.

Construction of an immune-related ceRNA network in cervical cancer based on HPV E6 splicing.

Background: Cervical cancer is one of the leading causes of cancer-related deaths worldwide. The unspliced human papillomavirus (HPV) E6 plays an important role in tumor progression and immune regulation. Improved immunotherapy implementation might benefit from a better knowledge of HPV E6 splicing-related immune gene expressions and immunocyte infiltration in cervical cancer. This study aimed to identify the potential therapeutic and prognostic roles of unspliced/spliced E6 ratio (E6 ratio) in cervical cancer. Methods: Data from the TCGA were used to analyze the E6 condition and clinical information. Nomogram and K-M analysis were used to analyze assess the prognostic significance, IOBR was used to investigate immunological infiltrates. Functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A core module was taken from the competitive endogenous RNA (ceRNA) network and used to build a lncRNA-miRNA-mRNA network. QT-qPCR was used to detect the expression of genes. CCK-8, colony formation, wound healing and migration assays were used to detect cell functions. Results: Our study found that HPV E6 ratio had significantly correlation with overall survival. In cervical cancer, a high E6 ratio was adversely linked with infiltrating levels of aDC, M1 macrophages, monocytes, NKT, and Tgd. High E6 ratio phenotypes were shown to be implicated in immune response regulation, cell adhesion, and Wnt signaling pathways, according to functional enrichment analysis. Subsequently, we constructed an immune-related ceRNA network based on E6 splicing in cervical cancer, including three lncRNA (LINC00943, LIFR-AS1, DANT2, and RASSF8-AS1), four miRNA (miR-205-5p, miR-181d-5p, miR-222-3p, and miR-221-3p), and seven mRNA (FGFR1, PRLR, CXCL2, ISG20, ISG15, SDC1, and NR2F2). Among them, CXCL2, SDC1, and miR-221-3p were associated with survival and immune cell infiltration. Conclusions: These data imply that a high E6 ratio in cervical cancer contributes to the immune-related ceRNA network, resulting in a low amount of infiltrating effector immune cells and tumor growth. As a result, the E6 ratio might be employed as a biomarker in cervical cancer to determine prognosis and treatment success.

Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.

Historically, immunotherapies have only resulted in a partial response from patients with advanced ovarian cancer, resulting in poor clinical efficacy. A full understanding of immune-related gene expression and immunocyte infiltration in ovarian cancer would be instrumental for the improved implementation of immunotherapy. The Capping Actin Protein, Gelsolin-Like (CAPG) gene encodes an actin-regulatory protein, which plays important roles in tumor progression and immune regulation. This study is aimed at identifying the potential therapeutic and prognostic roles of CAPG in ovarian cancer. CAPG expression and clinical information were investigated in the data collected from TCGA, Oncomine, GEPIA, UALCAN, and Kaplan-Meier plotter. CAPG coexpression networks were evaluated by LinkedOmics, GeneMANIA, and NetworkAnalyst. The correlation of CAPG with immune infiltrates was analyzed via TIMER, ImmuCellAI, and GEPIA. Our result showed that patients with high tumoral CAPG expression had significantly shorter 5-year overall survival. Functional enrichment analysis indicated that CAPG-related phenotypes were largely involved in inflammatory response, chemokine and cytokine signaling, cell adhesion, and Toll-like receptor signaling pathways. CAPG expression was positively correlated with infiltrating levels of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and exhausted T cells (Texs) while being negatively correlated with infiltrating levels of natural killer T cells (NKTs) and neutrophils in ovarian cancer. Moreover, the expression of FOXP3, CD25, CD127, CCR8, and TGFß in respect to Tregs; CCL2 and CD68 in respect to TAM; CD163, VSIG4, and MS4A4A in respect to M2 macrophages; CD33 and CD11b in respect to myeloid-derived suppressor cells (MDSCs); and PD1, CTLA4, LAG3, TIM3, GZMB, 2B4, and TIGIT in respect to Texs was significantly correlated with CAPG expression in ovarian cancer. These findings suggest that CAPG may contribute to the immunosuppressive tumor microenvironment in ovarian cancer, leading to an exhausted T cell phenotype and tumor progression. Therefore, CAPG can be used as a potential biomarker for determining prognosis and immunotherapy effectiveness in ovarian cancer.

Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro.

The type-1 insulin-like growth factor receptor (IGF-1R) is over-expressed by endometrial carcinoma, level of IGF-1R has been correlated with tumor progression, and high IGF-1R expression has been found to be an important prognostic factor. In the study, we used lentivirus-mediated shRNA targeting IGF-1R to silence its expression, then assessed the effect of down-regulation of this receptor on cell growth and chemosensitivity to cisplatin. Lentivirus-mediate shRNA was designed and transfected to the endometrial carcinoma HEC-1B cell. The IGF-1R mRNA and related protein expression, cell proliferation ability, cell apoptosis, and cell cycle change were detected. Cell proliferation inhibition rates, cell apoptosis, and level of cleaved caspase-9 were measured in various concentrations of cisplatin. The mRNA and protein level of IGF-1R, and the phosphorylated protein p-Akt, p-Erk were all suppressed after transfection. Cell proliferation was inhibited in successive five days after transfection, the highest inhibition rate was 43.28 ± 3.55% on day 5. After transfection, 24.96 ± 1.05% cells were in G(2)/M phase, and cell apoptotic rate increased from 10.66 ± 0.08 to 19.92 ± 1.34%. In various concentrations of cisplatin, transfected cells proliferation was significantly inhibited which made the IC50 value drop from 21.85 uM to 10.58 uM. Incubation with different concentrations of cisplatin for 48 h, cells apoptotic rate increased to 41.92 ± 2.5, 31.13 ± 2.76, 22.21 ± 4.63%, respectively, which was accompanied with increased cleaved caspase-9 expression. Lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma.

Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma.

Folate (FOL) mediated poly-lactide-co-glycolide-polyethylene glycol nanoparticles (FOL-PEG-PLGA NPs) bearing paclitaxel (PTX) were prepared for the effective delivery of drug to endometrial carcinoma. The average size, zeta potential and encapsulation efficiency of FOL-targeted NPs were found to be around 220 nm, -30.43 mV and 95.6%. Cellular uptake was observed. The accumulation of FOL-targeted NPs depends on dual effects of passive and active targeting. The FOL-targeted PTX NPs showed a greater cytotoxicity against HEC-1A cancer cells in vitro and in vivo, which might be induced by apoptosis. H&E staining did not showed apparent tissue damage to liver and kidney of the mice after injecting NPs intravenously. These results suggest that the novel FOL-PEG-PLGA NPs could be a potential delivery system with excellent therapeutic efficacy for targeting the drugs to cancer cells.

CHFR suppression by hypermethylation sensitizes endometrial cancer cells to paclitaxel.

OBJECTIVE: Impairment of a cell cycle checkpoint is often associated with sensitivity to chemotherapeutic drugs. Here, we studied the correlations between the checkpoint with forkhead-associated and ring finger (CHFR) gene expression and responses to paclitaxel in endometrial cancer cells. METHODS: We cultured 6 endometrial cancer cell lines exposed to paclitaxel, studied the cell cytotoxicity, cell cycle distribution, CHFR expression, and methylation status before and after a demethylation agent (5-aza) treatment. CHFR was silenced by small interfering RNA (siRNA). Then we examined tumor growth and CHFR expression with paclitaxel alone or combined with 5-aza pretreatment in vivo. RESULTS: We found that HEC-1B, RL-952, and AN3CA cells were sensitive to paclitaxel. Moreover, CHFR was weakly expressed in these cells, whereas paclitaxel-resistant cells (ISH, HEC-1A, and KLE) had high CHFR expression. Then we found that restored expression of CHFR by demethylation decreased the sensitivity to paclitaxel in AN3CA cells. In addition, cells with CHFR demethylation resulted in G2/M phase arrest that induced to paclitaxel resistance. These results were confirmed again in small interfering RNA-transfected HEC-1A cells. Furthermore, in nude mice model, restored expression of CHFR by demethylation inhibited tumor growth and decreased sensitivity to paclitaxel. CONCLUSION: Our data suggest that CHFR suppression regulated by hypermethylation may sensitize endometrial cancer cells to paclitaxel, and CHFR may be a promising marker to predict the response of endometrial cancer to paclitaxel.

The role of an immune signature for prognosis and immunotherapy response in endometrial cancer.

Immunotherapy is a practical and promising treatment for advanced and recurrent endometrial cancer (EC). In this study, we identified an immune-related gene (IRG) signature to predict the overall survival (OS) and response to immune checkpoints inhibitors (ICIs) in patients with EC. The RNA expression profiles of EC were obtained from The Cancer Genome Atlas database and then were filtered for IRGs based on the Immport database. Using the conjoint Cox regression model, an immune signature consisting of seven risk IRGs (CBLC, PLA2G2A, TNF, NR3C1, APOD, TNFRSF18, and LTB) was developed. The immune signature was independent of other clinical factors and was superior to the traditional staging method for OS prediction in EC. Immunohistochemistry staining from the Human Protein Atlas database and quantitative real-time PCR analysis of EC samples were also performed to validate the expression levels of risk IRGs. By further analyzing the tumor microenvironment in EC, patients in the low-risk subgroup showed a higher immune cell infiltration status, which was associated with a better prognosis. Moreover, the tumor mutational burden and immunophenoscore analysis demonstrated that the low-risk subgroup was more sensitive to ICI-based immunotherapy. These findings might shed light on the development of targeted treatment and novel biomarkers for patients with EC.

Identification of the 11-lncRNA signatures associated with the prognosis of endometrial carcinoma.

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.

Classification of serous ovarian carcinoma based on immunogenomic profiling.

Treatment of serous ovarian cancer (SOC) remains a clinical challenge. Classification of SOC based on immunogenomic profiling is important for establishing immunotherapy strategies. We extracted RNA-seq data of SOC from TCGA-OV. The samples were ultimately classified into high immune (Immunity_H) group and low immune (Immunity_L) group based on the immunogenomic profiling of 29 immune signatures by using unsupervised machine learning methods and modified by multifaceted characterization of immune response. High immune group showed the lower tumor purity and higher anti-tumor immune activity, and the higher expressions of PDCD1, CD274 and CTLA4. Furthermore, the overall survival time and the progression-free interval were significantly longer in high-immun group. The differentially expressed genes were mainly enriched in some immune response related functional terms and PI3K-AKT signaling pathway. According to ImmuCellAI, the abundance of various T cell subtypes in high immune group were significantly higher than those in low immune group. This novel immunotyping shows promise for prognostic and immunotherapeutic stratification in SOC patients.

Pre-treatment thrombocytosis predicts prognosis of endometrial cancer: A meta-analysis of 11 studies.

The aim of the present meta-analysis study was to determine the association between pre-treatment thrombocytosis and prognosis of patients with endometrial cancer. Articles published prior to December 2018 containing information on platelet count and endometrial cancer were searched in the PubMed, Embase and the Cochrane Library databases. A platelet count of ≥350 or >400×109/l was considered to indicate thrombocytosis. Hazard ratios (HRs) with 95% CI were calculated using a random- or fixed-effects model to assess the strength of the associations. A Funnel plot and Egger's test were used to evaluate the publication bias and sensitivity analyses were performed to estimate the robustness of the present results by using Stata 13.0 software. A pooled analysis of 11 studies that met the inclusion criteria was performed, involving a total of 2,590 patients with endometrial cancer. The overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) time of patients with endometrial cancer who exhibited pre-treatment thrombocytosis were shorter than those in patients without pre-treatment thrombocytosis (OS, HR=2.25, 95% CI=1.26-4.00; PFS, HR=2.60, 95% CI=1.23-5.50; DFS, HR=2.23, 95% CI=1.45-3.42). However, pre-treatment thrombocytosis was not associated with disease-specific survival time in patients with endometrial cancer (HR=2.17, 95% CI=0.51-9.27; P=0.296). Subgroup analysis indicated that pre-treatment thrombocytosis was not associated with OS time in patients of Asian and European ethnicity. Furthermore, pre-treatment thrombocytosis (platelet count >400×109/l) was an independent predictor of OS, PFS and DFS regardless of the clinical stage.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: This study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer. METHOD: The electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger's test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results. RESULTS: Finally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((hazard ratio (HR) = 0.603, 95%CI = 0.350 - 1.038) and DFS (HR = 0.678, 95%CI = 0.242 - 1.904) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: HR = 0.431, 95%CI = 0.238 - 0.781, p = 0.006; DFS: HR = 0.300, 95%CI = 0.187 - 0.482, p < 0.001) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (relative risk (RR) = 3.240, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (RR = 0.452, 95% CI =0.230-0.890). CONCLUSION: These findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.