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Updated: Aug 23, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Clinical Significance and Immune Infiltration Analyses of the Cuproptosis-Related Human Copper Proteome in Gastric
Xiaohuan Tang1, Ting Guo1, Xiaolong Wu1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center Ward I, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
Background:
The human copper Cu proteome, also termed Cu-binding proteins (CBP), is responsible for transporting "free" Cu to the cell that is related to cuproptosis. However, their role in gastric cancer (GC) has not been reported.
Methods:
RNA expression data of 946 GC patients were collected. A series of machine learning and bioinformatic approaches were combined to build a CBP signature to predict survival and immune microenvironment and guide the priority treatment. Immunohistochemistry and multicolor immunofluorescence (mIF) in 1076 resection slides were used to verify immune features.
Results:
A CBP signature was constructed using the machine learning method from TCGA that classifies cases as CBP_low and CBP_high groups. Multivariable Cox analysis confirmed that the CBP signature was an independent prognostic factor in the training and validation cohorts. Additionally, GC patients with low CBPscores showed an increase in anti-tumor immune microenvironment, which was further verified by mIF in pathological resections following immunotherapy. Importantly, patients with low CBPscores had higher levels of TMB/MSI and responded well to immunotherapy.
Conclusions:
We conducted the first and comprehensive CBP analysis of GC patients and established a clinically feasible CBP signature for predicting survival and response to treatment, which will be helpful for guiding personalized medicine.
