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YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.
Geng, Zi-Han; Du, Jun-Xian; Chen, Yue-Da; Fu, Pei-Yao; Zhou, Ping-Hong; Qin, Wen-Zheng; Luo, Yi-Hong.
Afiliação
  • Geng ZH; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
  • Du JX; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China.
  • Chen YD; Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
  • Fu PY; Department of General Surgery, Zhongshan Hospital, Fudan University (Xiamen Branch), 361004, Xiamen, Fujian, China.
  • Zhou PH; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
  • Qin WZ; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China.
  • Luo YH; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China. zhou.pinghong@zs-hospital.sh.cn.
Cancer Cell Int ; 24(1): 71, 2024 Feb 12.
Article em En | MEDLINE | ID: mdl-38347631
ABSTRACT

OBJECTIVE:

Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1.

DESIGN:

Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments.

RESULTS:

Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues.

CONCLUSIONS:

Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Cancer Cell Int Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Cancer Cell Int Ano de publicação: 2024 Tipo de documento: Article