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P28GANK overexpression is associated with chemotherapy resistance and poor prognosis in ovarian cancer.

ABSTRACT: The non-ATPase regulatory subunit 10 of the human 26S proteasome (p28GANK) has been implicated in the tumorigenesis and progression of several types of malignant tumor. The aim of the present study was to detect the expression of p28GANK in ovarian cancer (OC) and investigate its association with the clinicopathological features and prognosis of OC. The expression levels of p28GANK were determined in 114 OC tissue samples and 30 normal ovarian tissue samples using immunohistochemistry. An association was observed between p28GANK overexpression and certain clinicopathological factors, including advanced International Federation of Gynecology and Obstetrics stage (P=0.042), residual tumor size (P=0.005) and response to chemotherapy (P<0.001). Furthermore, patients with high expression of p28GANK demonstrated worse overall survival (OS) and disease-free survival (DFS) rates compared with patients with low expression of p28GANK (both P<0.001). Multivariate Cox regression analysis revealed that overexpression of p28GANK was an independent prognostic factor of OS and DFS in patients with OC (P=0.013 and P=0.001, respectively). In summary, the current results indicate that p28GANK may be a predictive marker and a therapeutic target for OC.

SUBMITTER: Yu G

PROVIDER: S-EPMC6923998 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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p28GANK overexpression is associated with chemotherapy resistance and poor prognosis in ovarian cancer.

Yu Ge G Li Na N Wang Wei W Niu Ming M Feng Xiaoling X

Oncology letters 20191113 1

The non-ATPase regulatory subunit 10 of the human 26S proteasome (p28GANK) has been implicated in the tumorigenesis and progression of several types of malignant tumor. The aim of the present study was to detect the expression of p28GANK in ovarian cancer (OC) and investigate its association with the clinicopathological features and prognosis of OC. The expression levels of p28GANK were determined in 114 OC tissue samples and 30 normal ovarian tissue samples using immunohistochemistry. An associ ...[more]

PMID: 31897164

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Project description:PurposeOvarian cancer is a major type of gynecological malignancy which characterized by the chemoresistance, heterogeneity and highly metastasis. However, the mechanism underlying the progression of ovarian cancer remains elusive. Pyruvate dehydrogenase kinase family plays critical roles in tumorigenesis, and PDK4 has been demonstrated to be an oncogene in many types of cancers. The aim of this study was to identify the role of PDK4 in ovarian cancer.MethodsWe explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro-tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan- Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients' prognosis.ResultsOverexpression of PDK4 markedly promoted cell proliferation, invasion and tumor growth in vivo. Furthermore, PDK4 confers cell resistant to chemotherapy-induced apoptosis. Mechanically, we demonstrated that PDK4 induced stem-like traits. Meanwhile, PDK4 expression was significantly evaluated in ovarian cancer tissues compared to that in adjacent non-cancer tissues, and high expression of PDK4 was associated with poor overall survival and progression-free survival of ovarian cancer patients.ConclusionThese results identify a novel role of PDK4 in regulating cell stem-like trait, which directly enhances the cell proliferation, invasion and chemoresistance in ovarian cancer, and targeting PDK4 could be a potential approach for ovarian cancer treatments.

Dataset Information

P28GANK overexpression is associated with chemotherapy resistance and poor prognosis in ovarian cancer.

Publications

p28GANK overexpression is associated with chemotherapy resistance and poor prognosis in ovarian cancer.

Similar Datasets

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