The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi‐omics study

Xu, Fangshi; Guan, Yawen; Xue, Li; Zhang, Peng; Li, Mingrui; Gao, Mei; Chong, Tie

doi:10.1002/cam4.4395

Cited by 39 publications

(32 citation statements)

References 51 publications

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“…Intriguingly, the ferroptosis driver and marker, TFRC was downregulated in SLC1A5-silencing tumors, whereas the ferroptosis suppressor SLC7A11 also appeared the same tendency. One possible reason was that Fe ion and cystine that relied on TFRC and SLC7A11 transport were essential for tumor growth ( Thévenod 2018 ; Xu et al, 2021a ; Koppula et al, 2021 ). Briefly, targeting SLC1A5 showed promising potentials in PC treatment.…”

Section: Resultsmentioning

confidence: 99%

“…For example, NCOA4, a ferritinophagy regulatory gene, leads to unfavorable prognosis and defective immune cell infiltration in renal cancer ( Mou et al, 2021 ). SLC7A11, a cystine/glutamate antiporter, not only enhances cervical cancer progression by circEPSTI1-miR-375-SLC7A11 axis ( Wu et al, 2021 ) but also serves as an unfavorable prognostic biomarker in renal carcinoma ( Xu et al, 2021a ). Alternatively, SLC1A5 has been identified as a positive modulator of ferroptosis ( Cao and Dixon 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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SLC1A5 Prefers to Play as an Accomplice Rather Than an Opponent in Pancreatic Adenocarcinoma

Wang

Pei

et al. 2022

Front. Cell Dev. Biol.

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Background: SLC1A5, a ferroptosis regulator gene, plays a dual role in cancer regulation. However, the roles of SLC1A5 in pancreatic adenocarcinoma (PAAD) remain elusive.Methods: SLC1A5’s expression and somatic mutation information were determined by TCGA, GEO, Oncomine, and cBioPortal databases. Its prognostic value was assessed in TCGA cohort and was validated in three independent cohorts. The effects of SLC1A5 on the tumor immune microenvironment were analyzed by the CIBERSORT algorithm, ssGSEA method, and TISIDB and TIMER databases. The “oncoPredict” R package, TIDE algorithm, ImmuCellAI online tool, and GSE35141 and GSE59357 datasets were used to ascertain its therapeutic correlations. GSEA and Western blot were applied to reveal the effects of SLC1A5 on the mTORC1 signaling pathway and ferroptosis process. The biofunctions of SLC1A5 were assessed by MTT, wound-healing, Transwell, and xenograft assays.Results: SLC1A5 was significantly upregulated in the PAAD samples but was not commonly accompanied with somatic mutation (2.3%). Overexpression of SLC1A5 led to a poor prognosis and was identified as an independent prognostic factor. Moreover, high SLC1A5 expression suppressed the antitumor immune process by changing the infiltrating levels of immune cells. As for therapeutic correlations, SLC1A5 was related to the efficacy of dasatinib, sunitinib, sorafenib, and imatinib but may not predict that of radiotherapy, chemotherapeutic drugs, and immune checkpoints inhibitors (ICIs). Notably, the overexpression of SLC1A5 could activate the mTORC1 signaling pathway and may increase the cellular sensitivity to ferroptosis. Finally, the overexpression of SLC1A5 markedly promoted proliferation, migration, and invasion of pancreatic cancer cells. At the in vivo level, SLC1A5 deletion inhibited tumor growth in a mice xenograft model.Conclusions: SLC1A5 prefers to play as an accomplice rather than an opponent in PAAD. Our findings provide novel insights into PAAD treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SLC1A5 Prefers to Play as an Accomplice Rather Than an Opponent in Pancreatic Adenocarcinoma

Wang

Pei

et al. 2022

Front. Cell Dev. Biol.

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“…In the past few years, several studies have reported that the regulation of FRGs can affect the process and the prognosis of ccRCC (33,34). But to our knowledge, there are still not enough studies on the correlation of FRGs with the prognosis and the treatment of ccRCC patients, and most of these studies only focus on a single FRG (18,19). Therefore, constructing an FRGs-based, accurate stratified model to allow for prognosis and treatment stratification of ccRCC patients will have important clinical significance.…”

Section: Discussionmentioning

confidence: 99%

“…However, a lot of details between FRGs and ccRCC patients remain unknown. Most studies focus on a single gene such as SLC7A11 and PRAS40 (18,19). Therefore, there is an urgent need to develop a ccRCC patient stratified model based on FRGs to measure the prognosis and treatment sensitivity, so as to help timely intervention and individualized treatment.…”

Section: Introductionmentioning

confidence: 99%

A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification

Sun

et al. 2022

Front. Oncol.

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IntroductionClear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC.Materials and MethodsThe mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay.ResultsIn this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC.ConclusionIn this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment.

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“…For example, an innovative NRF2 nano-modulator induces lung cancer ferroptosis and elicits an immunostimulatory tumor microenvironment 13 . SLC7A11 promoted the proliferation, migration, and invasion of renal cancer cells by enhancing GPX4 output, which in turn inhibits ferroptosis 14 . Therefore, targeting ferroptosis may be a new strategy for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Expression of ferroptosis-related gene correlates with immune microenvironment and predicts prognosis in gastric cancer

Song

Shu

2022

Sci Rep

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The study is to explore the role of ferroptosis-related genes (FRGs) in the occurrence and development of gastric cancer (GC), and to construct a new prognosis signature to predict the prognosis in GC. Clinical information and corresponding RNA data of GC patients were downloaded from TCGA and GEO databases. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, CIBERSORT, McpCounter and TIMER algorithm were used to analyze the infiltration of immune cells in two molecular subgroups. LASSO algorithm and multivariate Cox analysis were used to construct a prognostic risk signature. Functional analysis was conducted to elucidate the underlying mechanisms. Finally, the FRPGs were verified by Quantitative Real-Time PCR. We obtained 16 FRGs and divided GC patients into two subgroups by consistent clustering. Cluster C1 with a higher abundance of immune cell infiltration but lower probability in response to immunotherapy, it was reasonable to speculate that Cluster C1 was in accordance with the immune rejection type. Functional analysis showed that the biological process of DEGs in training cohort mainly included immune globulin, and human immune response mediated by circulating immune globulin. GSEA analysis showed that compared with Cluster C2, Cluster C1 showed lower expression in lipid metabolism. The nomogram combined with risk signature and clinical features can accurately predict the prognosis of GC patients. We identified two molecular subtypes, Clusters C1 and C2. In Cluster C1, patients with poor prognosis present with a hyperimmune status and low lipid metabolism, and we speculate that Cluster C1 was in accordance with the immune rejection type. The risk model based on FRPGs can accurately predict the prognosis of GC. These results indicated that ferroptosis is associated with TIME, and deserved considerable attention in determining immunotherapy treatment strategy for GC patients.

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The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi‐omics study

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 39 publications

References 51 publications

SLC1A5 Prefers to Play as an Accomplice Rather Than an Opponent in Pancreatic Adenocarcinoma

SLC1A5 Prefers to Play as an Accomplice Rather Than an Opponent in Pancreatic Adenocarcinoma

A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification

Expression of ferroptosis-related gene correlates with immune microenvironment and predicts prognosis in gastric cancer

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