Cuproptosis Subtyping System for Gastric Cancer
A new study has identified two gene expression subtypes of gastric cancer based on the activity of cuproptosis, a type of programmed cell death. Patients could be divided into two subtypes based on cuproptosis activity levels: CA-H, which had higher cuproptosis activity and better overall survival, and CA-L, which had lower cuproptosis activity and worse overall survival. The study also investigated the clinical significance and potential predictive value of the CRGS risk score signature in gastric cancer. The cuproptosis subtyping system may be a valuable tool for predicting the prognosis of gastric cancer patients and identifying those who may benefit from immunotherapy.
Gastric cancer (GC) is a common and deadly form of cancer, and while progress has been made in cancer management, new treatment strategies are still urgently needed. Resistance to cell death is a hallmark of cancer, and programmed cell death (PCD) is a target for cancer treatment. Apoptosis was the first PCD mode identified, but other modes, including cuproptosis, have been discovered.
New study identifies gene expression subtypes of gastric cancer based on cuproptosis activity and predicts patient survival and response to immunotherapy
A new study used publicly available datasets of single-cell expression and bulk RNA-seq profiles, as well as clinical information from five GC cohorts, which were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The researchers established a CRGS gene set comprising 13 key regulatory genes for cuproptosis and extracted five cuproptosis-related Gene Ontology gene sets. The study also evaluated the sensitivity of GC patients to ICB treatment.
The study identifies two gene expression subtypes of GC based on the activity of cuproptosis. The researchers used single-cell RNA sequencing data to assess the alteration of cuproptosis activity during GC initiation, and they found that cuproptosis activities were correlated with the severity of precancerous lesions and remained highly activated in the cancer stage. Patients could be divided into two subtypes based on cuproptosis activity levels: CA-H, which had higher cuproptosis activity and better overall survival, and CA-L, which had lower cuproptosis activity and worse overall survival. The study also investigated the clinical significance, somatic variation landscape, and potential predictive value of the CRGS risk score signature in GC.
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.
A promising prognostic and predictive biomarker for gastric cancer patients
The cuproptosis subtyping system can be used as a prognostic and predictive biomarker for GC. Patients with the high-risk signature had adverse prognoses and were associated with higher immune and stromal content in the tumor microenvironment, while patients with the low-risk signature had more favorable clinical outcomes and higher sensitivity to immunotherapy. The study also identified several immune cells associated with the high-risk signature, including activated NK cells, T cells, and myeloid cells, which may be involved in the development and progression of GC.
The cuproptosis subtyping system may be a valuable tool for predicting the prognosis of GC patients and for identifying those who may benefit from immunotherapy. It also provides insights into the biology of GC and the mechanisms underlying the NAG-CAG-IM-EGC progression cascade, providing a reference for future mechanistic studies.