Identification of Novel Immunologic Checkpoint Gene Prognostic Markers for Ovarian Cancer.

Ovarian cancer has a higher resistance to chemotherapy, displaying the highest mortality rate among gynecological cancers. Recently, immune checkpoint inhibitor therapy is an effective treatment for selected patients. However, a low response rate for immune checkpoint treatment was observed for ovarian cancer patients. Therefore, it is necessary to identify ovarian cancer patients who might gain benefits from immune checkpoint treatment. Datasets containing ovarian cancer samples with mRNA-seq and clinical follow-up data were downloaded from different databases like The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The researchers applied the univariate analysis for selecting the immune checkpoint genes (ICGs) at a significance level of P < 0.05 as the candidate ICGs. The Spearman correlation coefficients were calculated to compare the correlation between tumor mutation burden and candidate ICGs, and the Kaplan-Meier plots were generated. They also assessed the external validation datasets and the results of immunohistochemical staining. 46 and 35 ICGs were extracted from the TCGA and GEO datasets, respectively, and we categorized the ICGs into 3 expression patterns. Nine (TCGA) and three (GEO) ICGs were significantly related to the prognosis. Univariate survival analysis indicated a significant prognostic relationship between the expression levels of ICOS, TIGIT, and TNFRSF8 and overall survival (OS). Moreover, the expression of ICOS and TIGIT also presented a significantly positive relationship with the CD8A expression. Importantly, patients with a higher CD8A and ICOS expression level (ICOS-H/CD8A-H) showed a better survival rate compared to other patients. Stratified analysis using TIGIT, TNFRSF8, and CD8A expression also showed an improved prognosis for the high TIGIT/high CD8A expression subgroup and the low TNFRSF8/low CD8A expression subgroup compared to the other subgroups. This study identified different immune subtypes that can predict the OS of ovarian cancer patients. This data could prove to be beneficial for making important clinical decisions and designing individual immunotherapeutic strategies.

Identification of Tumor Microenvironment Scoring Scheme Based on Bioinformatics Analysis of Immune Cell Infiltration Pattern of Ovarian Cancer.

Background: Tumor microenvironment (TME) is the crucial mediator of tumor progression, and the TME model based on immune cell infiltration to characterize ovarian cancer is considered to be a promising strategy. Methods: Sample data of three ovarian cancer cohorts were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The scores of 22 kinds of immune cells were calculated based on CIBERSORT, and the TME clusters (TMECs) of ovarian cancer was determined by ConsensusClusterPlus. Genomic subtype was identified by non-negative matrix factorization (NMF). A TME scoring scheme was constructed using k-means algorithm and principal component analysis (PCA) to quantify the TME infiltration pattern of individuals. Results: Four TME subtypes of ovarian cancer samples were defined: TMEC1, TMEC2, TMEC3, and TMEC4. There were also significant differences in overall survival (OS) among the four TMEC, and the OS of TMEC3 was the longest. The difference analysis of TMEC3 and the other three TMECs respectively identified the DEGs and took the intersection, and 585 DEGs were obtained. Two genomic subtypes were identified by NMF based on the expression of 585 genes, which were called GeneC1 and GeneC2. The TME scoring scheme constructed by k-means and PCA algorithm was used to calculate the TME score of ovarian cancer in TCGA. High-TME score was significantly correlated with shorter survival time, older age, lower immunoactivated molecules, and immune checkpoint gene expression. Conclusions: This study highlighted the complexity and diversity of TME infiltration patterns in ovarian cancer and constructed a set of TME scoring scheme to reveal TME infiltration patterns and provided new insights into the landscape of TME.

Clinicopathological characteristics and treatment of patients with high-grade endometrial stromal sarcoma: A retrospective study of 40 cases.

ABSTRACT: To investigate the clinicopathological characteristics of patients with high-grade endometrial stromal sarcoma (HG-ESS).The clinicopathological characteristics, treatments, and prognostic information of consecutive HG-ESS patients were collected from medical records and then evaluated.A total of 40 women were included in the analysis. The immunohistochemical profiles indicated that HG-ESS tumors tend to be locally or weakly positive for vimentin (100%) and CD10 (72.0%) but mostly negative for desmin (7.7%) and AE1/AE3 (9.1%). The progression-free survival intervals and the clinical benefit rates of patients receiving radiotherapy and/or chemotherapy were slightly longer and higher than those receiving simple observation (progression-free survival: 6 and 5 months vs 2 months; clinical benefit rate: 83.3% and 75.0% vs 28.6%). The 1-year disease-specific survival (DSS) rate was 62.7%. Tumor size, myometrial invasion, lymphovascular space invasion, cervical involvement, Federation International of Gynecology and Obstetrics (FIGO) stage, and residual disease all significantly affected the DSS rate (P < .001, =.002, <.001, =.004, <.001, and <.001, respectively). For patients with stage I disease, the 1-year DSS rate was as high as 91.7%, in contrast to 66.7%, 26.7%, and 0% for those with stage II, III, and IV disease, respectively.HG-ESS is associated with an adverse prognosis. FIGO stage could effectively predict the prognosis of patients with this lethal disease. Immunohistochemical markers, vimentin+/CD10+ (local or very weak), in combination with desmin-/AE1/AE3-, may be helpful for improving the diagnostic accuracy of this lethal condition. The therapeutic roles of adjuvant chemotherapy and radiotherapy warrant further investigation.

Identification of a Prognostic Signature for Ovarian Cancer Based on the Microenvironment Genes.

Background: Ovarian cancer is highly malignant and has a poor prognosis in the advanced stage. Studies have shown that infiltration of tumor microenvironment cells, immune cells and stromal cells has an important impact on the prognosis of cancers. However, the relationship between tumor microenvironment genes and the prognosis of ovarian cancer has not been studied. Methods: Gene expression profiles and SNP data of ovarian cancer were downloaded from the TCGA database. Cluster analysis, WGCNA analysis and univariate survival analysis were used to identify immune microenvironment genes as prognostic signatures for predicting the survival of ovarian cancer patients. External data were used to evaluate the signature. Moreover, the top five significantly correlated genes were evaluated by immunohistochemical staining of ovarian cancer tissues. Results: We systematically analyzed the relationship between ovarian cancer and immune metagenes. Immune metagenes expression were associated with prognosis. In total, we identified 10 genes related to both immunity and prognosis in ovarian cancer according to the expression of immune metagenes. These data reveal that high expression of ETV7 (OS, HR = 1.540, 95% CI 1.023-2.390, p = 0.041), GBP4 (OS, HR = 1.834, 95% CI 1.242-3.055, p = 0.004), CXCL9 (OS, HR = 1.613, 95% CI 1.080 -2.471, p = 0.021), CD3E (OS, HR = 1.590, 95% CI 1.049 -2.459, p = 0.031), and TAP1 (OS, HR = 1.766, 95% CI 1.163 -2.723, p = 0.009) are associated with better prognosis in patients with ovarian cancer. Conclusion: Our study identified 10 immune microenvironment genes related to the prognosis of ovarian cancer. The list of tumor microenvironment-related genes provides new insights into the underlying biological mechanisms driving the tumorigenesis of ovarian cancer.

Evaluation of Cervical High-Grade Squamous Intraepithelial Lesions-Correlated Markers as Triage Strategy for Colposcopy After Co-Testing.

BACKGROUND: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. METHODS: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30-60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist. RESULTS: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. CONCLUSION: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.

Identification of a Six-Gene Signature for Predicting the Overall Survival of Cervical Cancer Patients.

BACKGROUND: Although the incidence of cervical cancer has decreased in recent decades with the development of human papillomavirus vaccines and cancer screening, cervical cancer remains one of the leading causes of cancer-related death worldwide. Identifying potential biomarkers for cervical cancer treatment and prognosis prediction is necessary. METHODS: Samples with mRNA sequencing, copy number variant, single nucleotide polymorphism and clinical follow-up data were downloaded from The Cancer Genome Atlas database and randomly divided into a training dataset (N=146) and a test dataset (N=147). We selected and identified a prognostic gene set and mutated gene set and then integrated the two gene sets with the random survival forest algorithm and constructed a prognostic signature. External validation and immunohistochemical staining were also performed. RESULTS: We obtained 1416 differentially expressed prognosis-related genes, 624 genes with copy number amplification, 1038 genes with copy number deletion, and 163 significantly mutated genes. A total of 75 candidate genes were obtained after overlapping the differentially expressed genes and the genes with genomic variations. Subsequently, we obtained six characteristic genes through the random survival forest algorithm. The results showed that high expression of SLC19A3, FURIN, SLC22A3, and DPAGT1 and low expression of CCL17 and DES were associated with a poor prognosis in cervical cancer patients. We constructed a six-gene signature that can separate cervical cancer patients according to their different overall survival rates, and it showed robust performance for predicting survival (training set: p ˂ 0.001, AUC = 0.82; testing set: p ˂ 0.01, AUC = 0.59). CONCLUSION: Our study identified a novel six-gene signature and nomogram for predicting the overall survival of cervical cancer patients, which may be beneficial for clinical decision-making for individualized treatment.

Inguinal endometriosis: Ten case reports and review of literature.

BACKGROUND: To describe the characteristics, diagnosis and surgical treatment of inguinal endometriosis (IEM). CASE SUMMARY: We retrospectively analyzed 10 patients diagnosed with IEM at Beijing Chao-Yang Hospital from 2011 to 2019. Relevant features, symptoms, images, surgical treatment, hormonal therapy and follow-up were collected and discussed. A total of 10 cases of IEM diagnosed by surgery and pathology were characterized by a lesion on the right side (9/11); five patients had symptoms related to the menstrual cycle, and only 3 patients were clearly diagnosed before surgery. Ultrasonography was of little assistance in confirming the diagnosis, but magnetic resonance imaging showed specific, high-intensity patterns. Anatomically, most of the IEM lesions were located in the extraperitoneal ligament (10/11); nine patients had inguinal hernias (IH), five had concurrent or prior pelvic endometriosis, and four had infertility. The clinical results from extensive resection were satisfactory. CONCLUSION: IEM is an extremely rare condition that can easily be misdiagnosed prior to surgery. A right IH may contribute to the formation of right-sided IEM, and extensive resection involving the round ligament and hernia sac is essential to prevent recurrence.

CYP27B1 Downregulation: A New Molecular Mechanism Regulating EZH2 in Ovarian Cancer Tumorigenicity.

BACKGROUND: Ovarian cancer has the highest mortality rate among gynecologic cancers, and most patients are diagnosed in advanced stages. Enhancer of zeste homolog 2 (EZH2) is a major tumor marker and an effective therapeutic target for ovarian cancer, but the underlying molecular mechanism remains unclear. The present study investigated the biological effects of EZH2 knockout in SKOV3 cells in vitro and in vivo and explored the molecular mechanism by integrated analysis of messenger RNA sequencing (mRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data. METHODS: The CRISPR/Cas9 system was used to establish EZH2 knockout SKOV3 cells. Protein expression was evaluated by Western blotting. The effect of EZH2 on ovarian cancer was evaluated in vitro with MTT, wound healing, Transwell, and apoptosis assays and in vivo with a xenograft model. mRNA-seq and ChIP-seq were performed to explore the molecular mechanism underlying the biological function of EZH2. Immunohistochemical staining (IHC) of tissue arrays was used to analyze the correlations among EZH2 and CYP27B1 expressions and prognosis. RESULTS: We obtained three EZH2 knockout subclones. EZH2 knockout SKOV3 cells exhibited significantly suppressed proliferation, migration, and invasion and a significantly increased apoptosis rate. The subcutaneous tumor formation rate decreased from 100 to 0% in the EZH2 knockout group. Integrated analysis of the mRNA-seq and ChIP-seq data identified 1,455 significantly upregulated genes with matching downregulated trimethylation of histone H3 lysine 27 (H3K27me3) methylation binding sites in 1b11H cells compared to SKOV3 cells. The set of downregulated genes in EZH2 knockout cells was highly enriched in genes regulating the activation of steroid biosynthesis; the top-ranked hub gene was CYP27B1. The EZH2 and CYP27B1 expression levels showed a statistically significant inverse correlation, which was also associated with unfavorable prognosis. The in vitro experiment demonstrated that CYP27B1 can suppress the proliferation, migration, and invasion of ovarian cancer cells. Moreover, the levels of AKT and p-AKT were significantly increased, whereas STAT3 was downregulated, in 1b11H cells compared to SKOV3 cells. Moreover, STAT3 and AKT overexpression was observed in 1b11H siRNA for CYP27B1 (siCYP27B1) cells. CONCLUSION: EZH2 plays an important role in promoting cell proliferation, migration, and invasion in ovarian cancer by regulating the core steroid biosynthesis gene via H3K27me3 methylation. Moreover, CYP27B1, the steroid biosynthesis hub gene, might be a novel therapeutic target for ovarian cancer.

Clinical and Expression Significance of AKT1 by Co-expression Network Analysis in Endometrial Cancer.

Introduction: Endometrial cancer is one of the most common uterine cancers worldwide. AKT is reported to regulate progesterone receptor B dependent transcription and angiogenesis in endometrial cancer. However, the potential mechanisms of AKT in the tumor progression of endometrial cancer remain unclear. Methods: We used GSE72708 with gene expression profiles of AKT regulation from the GEO database. We performed GSEA analysis to explore pathway enrichments. We found that most upregulated enriched pathways in siAKT group were associated with acid metabolism and immune network. Endometrial cancer and various signaling pathways were downregulated enriched. Moreover, different molecular mechanism of regulation between progestin (R5020) and AKT was identified, which were related to VEGF signaling pathway. The hub genes were evaluated by immunohistochemical staining of endometrial cancer tissues. Results: We screened out a total of 623 differentially expressed genes among different groups. According to weighted gene co-expression network analysis (WGCNA) method, four distinct modules were identified. We found brown module showed a very high positive correlation with siAKT group and a very high negative correlation with R5020 group. A total of six hub genes including PBK, BIRC5, AURKA, GTSE1, KNSTRN, and PSMB10 were finally identified associated with AKT1. In addition, the data also shows that the higher expression of AKT1, GTSE1, BIRC5, AURKA, and KNSTRN is significantly associate with poor prognosis of endometrial cancer. Conclusion: Our study identified six hub genes related to the prognosis of endometrial cancer, which may provide new insights into the underlying biological mechanisms driving the tumorigenesis of endometrial cancer, especially in AKT1 regulation.

Identification of a Prognostic Signature Associated With DNA Repair Genes in Ovarian Cancer.

Introduction: Ovarian cancer is a highly malignant cancer with a poor prognosis. At present, there is no accurate strategy for predicting the prognosis of ovarian cancer. A prognosis prediction signature associated with DNA repair genes in ovarian cancer was explored in this study. Methods: Gene expression profiles of ovarian cancer were downloaded from the GEO, UCSC, and TCGA databases. Cluster analysis, univariate analysis, and stepwise regression were used to identify DNA repair genes as potential targets and a prognostic signature for ovarian cancer survival prediction. The top genes were evaluated by immunohistochemical staining of ovarian cancer tissues, and external data were used to assess the signature. Results: A total of 28 DNA repair genes were identified as being significantly associated with overall survival (OS) among patients with ovarian cancer. The results showed that high expression of XPC and RECQL and low expression of DMC1 were associated with poor prognosis in ovarian cancer patients. The prognostic signature combining 14 DNA repair genes was able to separate ovarian cancer samples associated with different OS times and showed robust performance for predicting survival (Training set: p < 0.0001, AUC = 0.759; Testing set: p < 0.0001, AUC = 0.76). Conclusion: Our study identified 28 DNA repair genes related to the prognosis of ovarian cancer. Using some of these potential biomarkers, we constructed a prognostic signature to effectively stratify ovarian cancer patients with different OS rates, which may also serve as a potential therapeutic target in ovarian cancer.

Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data.

Endometrial cancer is highly malignant and has a poor prognosis in the advanced stage, thus, prediction of its prognosis is important. DNA methylation has rapidly gained clinical attention as a biomarker for diagnostic, prognostic and predictive purposes in various cancers. In present study, differentially methylated positions and differentially expressed genes were identified according to DNA methylation and RNA-Seq data. Functional analyses and interaction network were performed to identify hub genes, and overall survival analysis of hub genes were validated. The top genes were evaluated by immunohistochemical staining of endometrial cancer tissues. The gene function was evaluated by cell growth curve after knockdown CDC20 and CCNA2 of endometrial cancer cell line. A total of 329 hypomethylated highly expressed genes and 359 hypermethylated lowly expressed genes were identified, and four hub genes were obtained according to the interaction network. Patients with low expression of CDC20 and CCNA2 showed better overall survival. The results also were demonstrated by the immunohistochemical staining. Cell growth curve also demonstrated that knockdown CDC20 and CCNA2 can suppress the cell proliferation. We have identified two aberrantly methylated genes, CDC20 and CCNA2 as novel biomarkers for precision diagnosis in EC.

Progress in immunocytochemical staining for cervical cancer screening.

Cervical cancer is one of the most common gynecological malignancies. In recent years, the implementation of cervical cancer screening has resulted in the effective control of cervical cancer incidence. However, many deficiencies still exist in the current screening techniques and strategies. With advancements in cervical cancer screening research, immunochemical staining to determine cervical cytology has shown a broader application prospect in the early screening for cervical cancer, especially for triage in cervical cancer screening.

Piver Type II vs. Type III Hysterectomy in the Treatment of Early-Stage Cervical Cancer: Midterm Follow-up Results of a Randomized Controlled Trial.

Introduction: With the expansion of value-based medicine, we explore whether using type III hysterectomy to treat low-risk, early-stage cervical cancer constitutes overtreatment. In present study, we evaluate the midterm safety and postoperative quality of life of patients who underwent type II hysterectomy vs. type III hysterectomy with systematic lymphadenectomy for low-risk early-stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) IA2-IB1; maximum tumor diameter < 2 cm). Patients and methods: The main study was a multicenter, phase III, randomized controlled trial (NCT02368574, https://www.clinicaltrials.gov/ct2/show/NCT02368574). Patients meeting the criteria were randomly divided into type II and type III hysterectomy groups between 2015 and 2018. Midterm outcomes were analyzed at 36 months after the first eligible patient was enrolled. The primary end point was disease-free survival, and the secondary end point was postoperative quality of life. Results: A total of 97 patients were preliminarily enrolled, 93 of whom were included in the final analysis. The general information of the two groups did not differ. The 2-year DFS rate in the type II group was 100% compared with 97.9% in the type III group (P > 0.05). Compared to the type III group, the patients who underwent type II hysterectomy showed a shorter surgical time (163 ± 18.8 min vs. 226 ± 16.4 min, P = 0.014), less intraoperative blood loss (174 ± 27.7 ml vs. 268 ± 37.4 ml, P = 0.047), less postoperative urinary retention (5/46 vs. 11/47 cases, P = 0.109), and milder bladder injuries. The postoperative symptom experience scores of the type II group were significantly lower than those of the type III group. Moreover, the postoperative sexual/vaginal functioning and lubrication scores of the type II group were significantly lower than those of the type III group in subgroup analyses of patients who did not undergo postoperative chemoradiotherapy. Sexual apprehension scores were increased postoperatively in both groups. Conclusion: Based on the midterm analysis, the two groups show considerable security within 2 years after surgery, but long-term security requires further analysis. Type II hysterectomy can effectively reduce the surgical time and intraoperative blood loss, decrease postoperative complications, and improve the quality of life of early-stage cervical cancer patients.

Splenectomy during cytoreductive surgery in epithelial ovarian cancer.

BACKGROUND: The aim of the study was to analyze the underlying causes and application of splenectomy in patients with epithelial ovarian cancer (EOC) and assess its effect on the surgical satisfaction and prognosis of these patients. MATERIALS AND METHODS: Clinical data of patients with ovarian epithelial cancer treated with cytoreductive surgery were collected from 2000 to 2015 at Peking Union Medical College Hospital. RESULTS: A total of 2,882 patients underwent ovarian cancer cytoreductive surgery at Peking Union Medical College Hospital between 2000 and 2015, of whom 38 (1.3%) also underwent spleen resections. Of these 38 patients, one underwent splenectomy due to intraoperative trauma, whereas the remaining 37 patients underwent splenectomy due to splenic metastasis. Among these 37 patients, 27 underwent resection due to direct tumor spread in the spleen and 10 underwent resection due to hematogenous metastasis. For subsequent first-line chemotherapy, 22 patients were platinum sensitive and 15 were platinum resistant. Overall median survival and the postsplenectomy median survival time were 106 and 75 months, respectively. The overall median survival in secondary cytoreduction was 101 months compared with 20.3-56 months in literature reviews. Univariate analysis revealed that platinum resistance to first-line chemotherapy, suboptimal surgery, and hematogenous metastasis influenced survival. Chemosensitivity and residual disease were identified as independent risk factors by multivariate analysis. We also report a literature review concerning the efficacy and safety of splenectomy during cytoreductive surgery in EOC. CONCLUSION: Approximately 1.3% of patients with EOC underwent spleen resection during initial cytoreductive surgery and more often during recytoreductive surgery. Tumor involvement was the most common indication for splenectomy, and rare patients underwent splenectomy due to intraoperative trauma. Most patients achieved optimal surgery, and thus their overall survival and postsplenectomy survival rates were longer. The prognosis of patients was closely related to chemosensitivity and presence of residual tumors. Splenectomy should be attempted in all patients with splenic involvement in whom optimal cytoreductive surgery was achievable, no matter in primary or secondary cytoreduction.

Characterization of ovarian cancer cells and tissues by Fourier transform infrared spectroscopy.

BACKGROUND: Ovarian cancer is the most lethal of gynecological malignancies. Fourier Transform Infrared (FTIR) spectroscopy has gradually developed as a convenient, inexpensive and non-destructive technique for the study of many diseases. In this study, FTIR spectra of normal and several heterogeneous ovarian cancer cell lines as well as ovarian cancer tissue samples were compared in the spectral region of 4000 cm- 1 - 600 cm- 1. METHODS: Cell samples were collected from human ovarian surface epithelial cell line (HOSEpiC) and five ovarian cancer cell lines (ES2, A2780, OVCAR3, SKOV3 and IGROV1). Validation spectra were performed on normal and cancerous tissue samples from 12 ovarian cancer patients. FTIR spectra were collected from a NICOLET iN10 MX spectrometer and the spectral data were analyzed by OMNIC 8.0 software. RESULTS: Spectral features discriminating malignant tissues from normal tissues were integrated by cell line data and tissue data. In particular changes in cancerous tissues, the decrease in the amount of lipids and nucleic acids were observed. Protein conformation and composition were also altered in some cancer cells. The band intensity ratio of 1454/1400 was higher in normal cells/tissues and lower in cancer cells/tissues. CONCLUSION: The spectral features revealed the important molecular characteristics about ovarian cancer cells/tissues. These findings demonstrate the possible diagnostic use of FTIR spectroscopy, providing the research model and evidences, and supporting the future study on more tissue samples to establish a data bank of spectra features for the possible discrimination of ovarian cancers.

Grifolin induces apoptosis and promotes cell cycle arrest in the A2780 human ovarian cancer cell line via inactivation of the ERK1/2 and Akt pathways.

Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been demonstrated to possess antitumor activities in a variety of malignant cells. However, the signaling pathways and the molecular mechanisms underlying the anticancer effects of the agent in human ovarian cancer remain to be elucidated. The aim of the present study was to examine the effect of grifolin treatment on the human ovarian cancer cell line, A2780. MTT and flow cytometry analysis were used to analyze the viability of A2780 cells following treatment with grifolin. Western blotting was used analyze the expression of apoptosis-associated and cell cycle arrest-associated proteins. The results of MTT assays and flow cytometry analysis revealed that grifolin suppressed cell viability, induced apoptosis and triggered cell cycle arrest. Western blotting revealed that grifolin treatment resulted in inactivation of protein kinase B (Akt) and extracellular signal-related kinase 1/2 (ERK1/2), accompanied by upregulation of Bcl-2 associated X, apoptosis regulator, cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase, and downregulation of B cell lymphoma-2, cyclin dependent kinase 4 and cyclinD1. The results of the present study indicated that grifolin had significant anti-cancer effects on the human ovarian cancer A2780 cells, which occurred via the Akt and ERK1/2 signaling pathways to at least a certain extent. These results demonstrate the therapeutic potential of grifolin as a treatment for ovarian cancer.

Forkhead transcription factor 1 inhibits endometrial cancer cell proliferation via sterol regulatory element-binding protein 1.

The morbidity and mortality associated with endometrial cancer (EC) has increased in recent years. Regarded as a tumor suppressor, forkhead transcription factor 1 (FOXO1) has various biological activities and participates in cell cycle progression, apoptosis and differentiation. Notably, FOXO1 also functions in the regulation of lipogenesis and energy metabolism. Lipogenesis is a feature of cancer and is upregulated in EC. Sterol regulatory element-binding protein 1 (SREBP1) is a transcription factor that is also able to regulate lipogenesis. Increased expression of SREBP1 is directly correlated with malignant transformation of tumors. A previous study demonstrated that SREBP1 was highly expressed in EC and directly resulted in tumorigenesis. However, the association between FOXO1 and SREBP1 in EC is not clear. In the present study, lentiviruses overexpressing FOXO1 were used in cell transfection and transduction. Cell viability assays demonstrated that the overexpression of FOXO1 was able to suppress cell proliferation significantly in Ishikawa and AN3 CA cell lines. In addition, FOXO1 overexpression significantly inhibited cell migration and invasion ability in vitro. In xenograft models, overexpression of FOXO1 suppressed cell tumorigenesis, and western blot analysis demonstrated that SREBP1 expression was markedly reduced in the FOXO1-overexpressing cells. It may therefore be concluded that FOXO1 is able to inhibit the proliferative capacity of cells in vitro and in vivo, in addition to the migratory and invasive capacities in vitro by directly targeting SREBP1.

Anti-Müllerian hormone levels in patients with gestational trophoblastic neoplasia treated with different chemotherapy regimens: a prospective cohort study.

PURPOSE: To assess the ovarian reserve of patients with gestational trophoblastic neoplasia (GTN) treated with chemotherapy by evaluating serum anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels before, during, and after chemotherapy. RESULTS: The basal AMH level (mean: 3.98 ± 3.20 ng/mL) negatively correlated with age, while the basal FSH level (mean: 5.71 ± 9.69 mIU/mL) had no correlation with age. After 3 chemotherapy cycles, serum AMH levels decreased and FSH levels increased. The magnitude of the AMH level decline was significantly greater for combination chemotherapy than for single-agent dactinomycin D therapy (61.80% vs. 27.57%) (p = 0.0004) and was higher in patients whose regimens included etoposide (73.69% vs 40.51%) (p = 0.0359). After chemotherapy completion, AMH levels showed a further decline, and cumulative AMH concentration change was associated with doses of vincristine (p = 0.009) and etoposide (p = 0.032). At the 3-month follow-up, AMH levels significantly increased in the dactinomycin D group (p = 0.0067). MATERIALS AND METHODS: This prospective study included 34 patients with GTN. Serum AMH and FSH levels were measured before chemotherapy, after the 3rd cycle, and at 2 weeks and 3 months after chemotherapy. Cumulative changes of serum AMH levels in patients who received different chemotherapy regimens were analyzed. CONCLUSIONS: Chemotherapy for GTN affects the ovarian reserve, with substantial differences between chemotherapy protocols. The results improve our understanding of ovarian toxicity and support the use of fertility preservation strategies.

Grifolin induces autophagic cell death by inhibiting the Akt/mTOR/S6K pathway in human ovarian cancer cells.

Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been reported to possess antitumor activities in various tumors. To date, no report exists on the role of autophagy in grifolin-treated human ovarian cancer cells. In the present study, we investigated the effect and the mechanism of autophagy in ovarian cancer. Ovarian cancer cell lines A2780 and SKOV3 were treated with grifolin. Cell proliferation was assessed by MTT assay and the autophagic effect was determined using flow cytometry, electron microscopy, immunofluorescence staining and GFP-LC3 puncta formation assay. The expression of autophagy markers and the main autophagy-associated Akt/mTOR/S6K pathway proteins were measured by western blot analysis. MTT assay indicated that grifolin inhibits the proliferation of human ovarian cancer cell lines A2780 and SKOV3. Flow cytometry, electron microscopy, immunofluorescence and GFP-LC3 puncta formation assay proved that grifolin induces autophagic cell death in human ovarian cancer. The results of the western blot analysis suggested that grifolin treatment leads to upregulation of autophagy markers LC3B, Atg7, Beclin-1 along with downregulation of P62. In addition, the proteins of the pathways p-Akt, p-mTOR, p-p70S6K and p-4E-BP1 were downregulated while the total of these proteins remained unaffected. The present study indicated that grifolin could induce autophagic cell death in human ovarian cancer by inhibiting the Akt/mTOR/S6K pathway.

Biglycan enhances the ability of migration and invasion in endometrial cancer.

OBJECTIVE: This study aimed to confirm that biglycan (BGN) can promote the migration and invasion in endometrial cancer both in vitro and in vivo and the possible therapeutic value of BGN in endometrial cancer. METHODS: Western blot was used to screen out the higher protein level of BGN in human endometrial cancer cells; BGN knocked down cells were constructed by lentiviral transfection; The effect of BGN in endometrial cancer detected by wound healing, transwell migration, and invasion, endothelial tube formation assay in vitro, and xenograft model in vivo. RESULTS: (1) We found that BGN expression level is higher in the Ishikawa (ISK, high differentiation) and AN3CA (poor differentiation) cells than other endometrial cancer cells. (2) BGN enhances endometrial cancer cell wound healing, invasion, and migration ability and formation ability of endothelial cells in vitro. Xenograft model has confirmed the outcome in vivo. CONCLUSIONS: BGN might play an important role on metastasis in human endometrial cancer and it might be a target marker for the molecular therapy of advanced and recurrence endometrial cancer.