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Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin.
Guo, Zhengyang; Huang, Jiaqi; Huo, Xiao; Huang, Chen; Yu, Xiaotong; Sun, Yan; Li, Yanfang; He, Tianhui; Guo, Hongyan; Yang, Jianling; Xue, Lixiang.
Afiliación
  • Guo Z; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
  • Huang J; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
  • Huo X; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
  • Huang C; Peking University Third Hospital Cancer Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China.
  • Yu X; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
  • Sun Y; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
  • Li Y; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
  • He T; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
  • Guo H; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
  • Yang J; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
  • Xue L; Cancer Center of Peking University Third Hospital, Beijing, 100191, China.
Sci China Life Sci ; 67(6): 1226-1241, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38300441
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cisplatino / Quimiocina CCL5 / Epóxido Hidrolasas / Microambiente Tumoral Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci China Life Sci Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cisplatino / Quimiocina CCL5 / Epóxido Hidrolasas / Microambiente Tumoral Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci China Life Sci Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China