Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,r...Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism disorder.As a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian cancer.Therefore,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes.This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the model.Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer.Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer.Additionally,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian cancer.These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.展开更多
Histone methylation plays a crucial role in tumorigenesis.Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase that regulates chromatin structure and gene expression.EZH2 inhibitors(EZH2is)have been shown t...Histone methylation plays a crucial role in tumorigenesis.Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase that regulates chromatin structure and gene expression.EZH2 inhibitors(EZH2is)have been shown to be effective in treating hematologic malignancies,while their effectiveness in solid tumors remains limited.One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment.Hypoxia-inducible factor 1-alpha(HIF-1α)is a key hypoxia responder that interacts with EZH2 to promote tumor progression.Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.展开更多
基金supported by the General Program of National Natural Science Foundation of China(82272745,82072870,81972966)General Program of Natural Science Foundation of Beijing(7202224)+2 种基金the National Key Research and Development Program of China(2022YFA1104001)Youth Program of National Natural Science Foundation of China(82203102,82303801)Peking University Third Hospital Clinical Key Project(BYSY2022069)。
文摘Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism disorder.As a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian cancer.Therefore,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes.This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the model.Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer.Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer.Additionally,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian cancer.These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.
基金funded by the National Key Research and Development Program of China(2022YFA1104001 to L.X.)the National Natural Science Foundation of China(82272745 and 81972966 to L.X.,82203433 to Y.W.,82303225 to Y.T.)+1 种基金the Peking University Third Hospital Clinical Key Project(BYSYZD2023010 to L.X.,BYSY2022070 to Y.W.,BYSYZD2023041 and BYSYRCYJ2023004 to J.Z.)the National Institutes of Health(R01 CA107469 and R01 CA125577 to C.G.K.).
文摘Histone methylation plays a crucial role in tumorigenesis.Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase that regulates chromatin structure and gene expression.EZH2 inhibitors(EZH2is)have been shown to be effective in treating hematologic malignancies,while their effectiveness in solid tumors remains limited.One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment.Hypoxia-inducible factor 1-alpha(HIF-1α)is a key hypoxia responder that interacts with EZH2 to promote tumor progression.Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.
