Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling

Xiang, Renshen; Song, Wei; Ren, Jun; Wu, Jing; Fu, Jincheng; Fu, Tao

doi:10.1186/s13287-021-02633-x

Cited by 9 publications

(9 citation statements)

References 62 publications

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“…S1E). Isolation of spheroid-forming cells is important to investigate cancer stemcell-related characteristics [19], and AGS and HGC-27 cells were cultured on 3D ultra-low attachment plates as spheroids for 14 days. Surprisingly, the mRNA levels of PTBP1, together with three pluripotency factors Oct4, Nanog and Sox2 were robustly elevated in spheroid cultures than in monolayer cultures of two GC cells, which were responsible for converting cancer cells from differentiated to a stem-cell-like state (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

Chu

et al. 2023

Br J Cancer

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Background Gastric cancer (GC) tumorigenesis and treatment failure are caused by cancer stem cells. Polypyrimidine tract binding protein 1 (PTBP1) was shown to be involved in the development of embryonic stem cells and is now being considered as a therapeutic target for tumour progression and stem-cell characteristics. Methods PTBP1 expression in GC samples was detected using tissue microarrays. Proliferation, colony formation, spheroid formation and stem-cell analysis were used to examine PTBP1’s role in tumorigenesis and stem-cell maintenance. In AGS and HGC-27 cells with or without PTBP1 deficiency, ubiquitin-related protein expression and co-precipitation assays were performed. Results We identified that PTBP1 was aberrantly highly expressed and represented a novel prognostic factor in GC patients. PTBP1 maintained the tumorigenic activity and stem-cell characteristics of GC in vitro and in vivo. PTBP1 directly interacts with c-Myc and stabilises its protein levels by preventing its proteasomal degradation. This is mediated by upregulating the ubiquitin-specific proteases USP28 and limiting FBW7-mediated ubiquitination of c-Myc. Moreover, the depletion of PTBP1-caused tumour regression was significantly compromised by exogenous c-Myc expression. Conclusions By preserving the stability of c-Myc through the ubiquitin–proteasome pathway, the oncogene PTBP1 supports stem-cell-like phenotypes of GC and is involved in GC progression.

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Section: Resultsmentioning

confidence: 99%

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

Chu

et al. 2023

Br J Cancer

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“…It performed well in both the training and validation cohorts. A previous study established a risk model based on prognostic DEGs between cancer stem cell subtypes in gastric cancer [ 39 ]. In this model, patients with lower risk scores were classified into cluster 1, which had the combined feature of higher immune activation and lower ferroptosis score compared with cluster 2.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis

Xie

Chen

2023

IJMS

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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis, joint damage and deformity. A newly described type of cell death, ferroptosis, has an important role in the pathogenesis of RA. However, the heterogeneity of ferroptosis and its association with the immune microenvironment in RA remain unknown. Synovial tissue samples from 154 RA patients and 32 healthy controls (HCs) were obtained from the Gene Expression Omnibus database. Twelve of twenty-six ferroptosis-related genes (FRGs) were differentially expressed between RA patients and HCs. Furthermore, the patterns of correlation among the FRGs were significantly different between the RA and HC groups. RA patients were classified into two distinct ferroptosis-related clusters, of which cluster 1 had a higher abundance of activated immune cells and a corresponding lower ferroptosis score. Enrichment analysis suggested that tumor necrosis factor-α signaling via nuclear factor-κB was upregulated in cluster 1. RA patients in cluster 1 responded better to anti-tumor necrosis factor (anti-TNF) therapy, which was verified by the GSE 198520 dataset. A diagnostic model to identify RA subtypes and immunity was constructed and verified, in which the area under the curve values in the training (70%) and validation (30%) cohorts were 0.849 and 0.810, respectively. This study demonstrated that there were two ferroptosis clusters in RA synovium that exhibited distinct immune profiles and ferroptosis sensitivity. Additionally, a gene scoring system was constructed to classify individual RA patients.

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“… 21–23 Using annotation files downloaded from TCGA database, the TMB value of each sample was estimated in Perl software. 14 We compared the TMB score differences between high- and low-risk patients. Spearman correlation analysis was also performed to test the correlation between TMB and risk scores.…”

Section: Methodsmentioning

confidence: 99%

“… 10–12 Our previous studies also corroborated that GC patients could be classified into different clusters based on the expression pattern of pyroptosis-related genes and enrichment level of stem-cell related gene sets. 13 , 14 Both of these subtyping approaches showed high accuracy in predicting the prognosis of GC patients and a strong correlation with the tumor microenvironment (TME).…”

Section: Introductionmentioning

confidence: 99%

Identification of Cuproptosis-Related Subtypes, Establishment of a Prognostic Signature and Characterization of the Tumor Microenvironment in Gastric Cancer

Li¹,

Kong²,

Song³

et al. 2023

IJGM

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Purpose Cuproptosis is a newly identified form of programmed cell death. We aimed to comprehensively discuss the correlation of cuproptosis with gastric cancer (GC) using bioinformatic methods. Patients and Methods This study selected GC bulk and single-cell RNA sequencing profiles from public databases. Based on the enrichment pattern of cuproptosis-related gene sets (CRGSs), GC patients were classified into different cuproptosis subtypes. A series of systematic analyses was performed to investigate the correlation of cuproptosis subtype with biological function and immune cell infiltration. In addition, we established a CRGS risk score signature to quantify GC patients’ risk level, and analyzed the signature’s relationship with clinical features, tumor microenvironment (TME) and treatment responses. Genes used for the construction of the risk score model were also detected in GC tumor and normal tissues by real-time quantitative polymerase chain reaction (RT-qPCR). Results First, analysis of scRNA-seq data revealed the alterations in CRGS enrichment scores for patients with GC and precancerous diseases. Then, based on large GC patient cohorts, two cuproptosis subtypes with significant differences in survival, biological function and TME were identified. Furthermore, we established a CRGS risk score signature. High-risk patients on the CRGS risk score signature with worse overall survival were characterized by higher immune and stromal contents in the TME, more advanced clinicopathological features, and better sensitivity to a wider range of anti-tumor drugs. Low-risk patients were correlated with higher tumor purity, and demonstrated more favorable clinical outcomes and higher sensitivity to immunotherapy. Conclusion The current work elucidated that cuproptosis plays an important role in the regulation of TME landscapes in GC. Two cuproptosis subtypes with distinct TME characteristics were identified. In addition, the establishment of a CRGS risk score signature could provide novel insights into accurate prediction and personalized treatment for GC patients.

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Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling

Cited by 9 publications

References 62 publications

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis

Identification of Cuproptosis-Related Subtypes, Establishment of a Prognostic Signature and Characterization of the Tumor Microenvironment in Gastric Cancer

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