Identification of a ferroptosis-related gene signature for predicting the prognosis of cholangiocarcinoma

Wang, Ziyi; Zhang, Yaodong; Chen, Yananlan; Liu, Shuochen; Li, Changxian; Li, Xiangcheng

doi:10.1080/17474124.2022.2029700

Cited by 7 publications

(8 citation statements)

References 53 publications

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“…In CCA, bioinformatics studies indicate that the ferroptosis-related gene signature can be used to predict the prognosis of CCA. 35,36 CCA stem-like cells have a higher basal iron content and increased ROS production. 10 Iron functions as a novel metabolic factor contributing to CCA growth and may have implications for a better therapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

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FBXO31 sensitizes cancer stem cells‐like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma

Zhu

Zheng

Huang

et al. 2022

Liver International

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Background & Aims Cholangiocarcinoma (CCA) is a malignant tumour originating from the biliary epithelium that easily infiltrates, metastasizes and recurs. The deficiency of FBXO31 facilitates the initiation and progression of several types of cancer. However, the involvement of FBXO31 in CCA progression has remained unclear. Methods qRT‐PCR was used to detect the expression of FBXO31 in CCA. The biological functions of FBXO31 were confirmed in vivo and in vitro. Sphere formation and flow cytometry were used to identify the stem cell properties of CCA. Results FBXO31 is downregulated in CCA and that deficiency of FBXO31 is associated with the TNM stage of CCA. Functional studies showed FBXO31 inhibits cell growth, migration, invasion, cancer stem cell (CSC) properties and epithelial‐mesenchymal transition (EMT) in vitro and impedes tumour growth in vivo. In addition, overexpression of FBXO31 increases the cisplatin (CDDP) sensitivity of CCA cells. RNA‐sequencing analysis revealed that FBXO31 is involved in redox biology and metal ion metabolism in CCA cells during CDDP treatment. Further studies revealed that FBXO31 enhances ferroptosis induced by CDDP in CCA and CSC‐like cells. FBXO31 enhances ubiquitination of glutathione peroxidase 4 (GPX4), which leads to proteasomal degradation of GPX4. Moreover, overexpression of GPX4 compromises the promoting effects of FBXO31 on CDDP‐induced ferroptosis in CCA and CSC‐like cells. Conclusions Our studies indicate that FBXO31 functions as a tumour suppressor in CCA and sensitizes CSC‐like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4.

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Section: Discussionmentioning

confidence: 99%

“…However, the role of ferroptosis in CCA has rarely been reported. In CCA, bioinformatics studies indicate that the ferroptosis‐related gene signature can be used to predict the prognosis of CCA 35,36 . CCA stem‐like cells have a higher basal iron content and increased ROS production 10 .…”

Section: Discussionmentioning

confidence: 99%

FBXO31 sensitizes cancer stem cells‐like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma

Zhu

Zheng

Huang

et al. 2022

Liver International

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“… 25 There are also several articles on prognostic gene signatures of ferroptosis in CHOL, but these articles do not delve into the possible mechanisms of ferroptosis in CHOL. 26 , 27 , 28 …”

Section: Discussionmentioning

confidence: 99%

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Yao

Liu

Tian

et al. 2022

Molecular Therapy - Oncolytics

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“…Recently, several prognostic gene signatures have been constructed for CCA (48). Wang et al identified a signature consisting of five ferroptosis-related genes for predicting the prognosis of cholangiocarcinoma (49). Wang et al created a thirteen-lncRNA prognostic signature for iCCA (50).…”

Section: Discussionmentioning

confidence: 99%

“…Wang et al. identified a signature consisting of five ferroptosis-related genes for predicting the prognosis of cholangiocarcinoma ( 49 ). Wang et al.…”

Section: Discussionmentioning

confidence: 99%

Identification of therapeutic targets and prognostic biomarkers in cholangiocarcinoma via WGCNA

Xiao

et al. 2022

Front. Oncol.

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BackgroundCholangiocarcinoma (CCA) is a highly aggressive malignant tumor for which limited treatment methods and prognostic signatures are available. This study aims to identify potential therapeutic targets and prognostic biomarkers for CCA.MethodsBased on differentially expressed genes (DEGs) identified from The Cancer Genome Atlas (TCGA) data, our study identified key gene modules correlated with CCA patient survival by weighted gene coexpression network analysis (WGCNA). Cox regression analysis identified survival-related genes in the key gene modules. The biological properties of the survival-related genes were evaluated by CCK-8 and transwell assays. Then, these genes were used to construct a prognostic signature that was internally and externally validated. Additionally, by combining clinical characteristics with the gene−based prognostic signature, a nomogram for survival prediction was built.ResultsWGCNA divided the 1531 DEGs into four gene modules, and the yellow gene module was significantly associated with overall survival (OS) and histologic neoplasm grade. Our study identified the lncRNA AGAP2−AS1 and a novel gene, GOLGA7B, that are closely related to survival. GOLGA7B downregulation promoted the invasion, migration and proliferation of CCA cells, but AGAP2−AS1 had the opposite effect. AGAP2−AS1 and GOLGA7B were integrated into a gene−based prognostic signature, and both internal and external validation studies confirmed that this two-gene prognostic signature and nomogram could accurately predict CCA patient prognosis.ConclusionAGAP2−AS1 and GOLGA7B are potential therapeutic targets and prognostic biomarkers for CCA.

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Identification of a ferroptosis-related gene signature for predicting the prognosis of cholangiocarcinoma

Cited by 7 publications

References 53 publications

FBXO31 sensitizes cancer stem cells‐like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma

FBXO31 sensitizes cancer stem cells‐like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Identification of therapeutic targets and prognostic biomarkers in cholangiocarcinoma via WGCNA

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