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.
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.
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.
BackgroundThe 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 methodsClinical data of patients with ovarian epithelial cancer treated with cytoreductive surgery were collected from 2000 to 2015 at Peking Union Medical College Hospital.ResultsA 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.ConclusionApproximately 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.
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.
Abstract. 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.
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.
BackgroundOvarian 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.MethodsCell 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.ResultsSpectral 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.ConclusionThe 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.
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