Ovarian carcinoma has the highest mortality among the malignant tumours in gynaecology, and new treatment strategies are urgently needed to improve the clinical status of ovarian carcinoma patients. The Cancer Genome Atlas (TCGA) cohort were performed to explore the immune function of the internal environment of tumours and its clinical correlation with ovarian carcinoma. Finally, four molecular subtypes were obtained based on the global immune‐related genes. The correlation analysis and clinical characteristics showed that four subtypes were all significantly related to clinical stage; the immune scoring results indicated that most immune signatures were upregulated in C3 subtype, and the majority of tumour‐infiltrating immune cells were upregulated in both C3 and C4 subtypes. Compared with other subtypes, C3 subtype had a higher BRCA1 mutation, higher expression of immune checkpoints, and optimal survival prognosis. These findings of the immunological microenvironment in tumours may provide new ideas for developing immunotherapeutic strategies for ovarian carcinoma.

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Introduction: Keratin 80 (KRT80) is a type II epithelial keratin protein that plays an important role in cell differentiation and tumor progression. However, its role and mechanisms in ovarian cancer remain unclear. Methods: The effect of KRT80 on the survival and prognosis of patients with ovarian cancer was determined using immunohistochemistry. Cell lines overexpressing KRT80 and with KRT80 knockdown were established to study its effect on the malignant behavior of ovarian cancer cells. Western blotting was used to detect changes in related molecules, and in the MEK/ERK signal transduction pathway. ChIP assay was used to confirm that ETS1 regulates KRT80 at the transcriptional level. A double luciferase assay was used to confirm the target of miR-206. Results: The expression levels of KRT80 were high in ovarian cancer tissue, and were related to survival and prognosis. KRT80 expression is an independent prognostic factor in patients with ovarian cancer. KRT80 overexpression promotes the proliferation of ovarian cancer cells, the transition from G1 phase to S phase, invasion, and migration. KRT80 overexpression increased the expression of BCL2/BAX, CyclinD1, MMP2, MMP9, and N-cadherin, decreased the expression of E-cadherin, and increased the phosphorylation of MEK and ERK. ETS1 binds to the upstream promoter sequence of KRT80 and regulates KRT80 expression at the transcriptional level. ETS1 is a direct target of miR-206 in ovarian cancer cells. Conclusion: KRT80 regulated by miR-206/ETS1 promotes tumor progression via the MEK/ERK pathway in ovarian cancer, and KRT80 may have applications as a screening biomarker and potential therapeutic target for ovarian cancer.

Background: Ovarian cancer is one of the common malignant tumors in gynecology. Although the treatment strategy for ovarian cancer has been greatly improved in recent years, due to the metastasis, recurrence and drug resistance, the 5-year overall survival rate of patients is still less than 47%. However, at present, there is no specific markers for clinical application. The purpose of this study is to verify the expression and clinical significance of KIF23 in ovarian cancer and identify potential targets for the clinical treatment of ovarian cancer. Methods: The expression of KIF23 in ovarian cancer tissues and its relationship between survival prognosis and clinical pathological parameters were analyzed in Oncomine, GEO, and TCGA databases. KIF23 expression was analyzed by Kaplan-Meier plotter database and its relationship with chemo-resistance was studied. The molecular mechanism involved in KIF23 was analyzed from the perspective of gene mutation, copy number variation and other genomics. Finally, immunohistochemistry experiment was used to verify the expression of KIF2, and its relationship between the clinical pathological parameters and prognosis of ovarian cancer patients was analyzed by single factor and multivariate Cox regression models. Results: Bioinformatic and experimental results have demonstrated that KIF23 is highly expressed in ovarian cancer, and its high expression is positively correlated with poor prognosis. Overexpression of KIF23 can cause chemotherapy resistance in ovarian cancer and affect the overall survival of patients. Genomics analysis showed that KIF23 expression was associated with mutations such as FLG2 and TTN, and it was significantly enriched in tumor signaling pathways such as DNA replication and cell cycle. Conclusions: KIF23 can not only be used as a biomarker of poor prognosis in patients with various stages of ovarian cancer, but also be used as a molecular targeted drug and an independent prognostic biomarker for the treatment of ovarian cancer patients.

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.