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

May 11, 2023International journal of general medicine

Types of Copper-Related Cell Death, Risk Prediction, and Tumor Environment Features in Stomach Cancer

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Abstract

Two subtypes with distinct characteristics were identified in gastric cancer (GC) patients.

Alterations in cuproptosis-related gene sets (CRGSs) were observed in patients with GC and precancerous diseases.
High-risk patients, determined by the CRGS risk score signature, exhibited worse overall survival and advanced clinical features.
High-risk patients had greater immune and stromal content in the (TME) and demonstrated better sensitivity to a wider range of anti-tumor drugs.
Low-risk patients were associated with higher tumor purity and showed more favorable clinical outcomes and greater sensitivity to immunotherapy.

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PURPOSE: 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, (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.

Key numbers

1274

High-Risk Patients

Total number of gastric cancer patients analyzed in the study.

<0.001

Overall Survival Difference

Statistical significance of overall survival differences between subtypes CA-H and CA-L.

0.731

AUC for 1-Year OS Prediction

Area under the curve for the nomogram predicting 1-year overall survival.

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

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