ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(6):1551-1567. doi:10.7150/jca.92327 This issue Cite
Research Paper
Cuproptosis-related genes score and its hub gene GCSH: A novel predictor for cholangiocarcinomas prognosis based on RNA seq and experimental analyses
1. Organ Transplant Centre, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
2. Department of Pathology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
3. Department of Surgical Anesthesiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
#Rui He, Yihu L and Pengcheng Jiao contributed equally to this work and should be considered co-first authors.
Abstract
Background: Recent researches have demonstrated that cuproptosis, a copper-dependent cell death mechanism, is related to tumorigenesis, progression, clinical prognosis, tumor microenvironment, and drug sensitivity. Nevertheless, the function and impact of cuproptosis in cholangiocarcinoma (CCA), remain elusive.
Methods: Utilizing data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA-CHOL) datasets, we conducted subgroup typing of CCA according to cuproptosis-related genes (CRGs) and explored functional differences and prognostic value between groups. A CRG score was established considering clinical prognosis and gene expression. Furthermore, differences in the immune microenvironment, response to immunotherapy, metabolic patterns, and cancer progression characteristics between high- and low-risk groups were examined on the basis of these scores. In vitro experiments validated the function of the key gene glycine cleavage system protein H (GCSH) in cellular and tissues, respectively.
Results: Prognostic models established on the basis of subgroup genetic differences achieved satisfactory results in validation. Metabolic-related gene expression levels and tumor microenvironment distribution were significantly different between the high and low CRG groups. GCSH was revealed as the singular prognostic CRG in CCA (HR =6.04; 95% CI: 1.15-31.80). Moreover, inhibition of the cupcoptosis key gene GCSH attenuated the malignant ability of CCA cell lines in vitro, including cell proliferation, migration and invasion, and this function of GCSH may be achieved via JAK-STAT signaling in CCA.
Conclusion: The CRG scoring system accurately predicts prognosis and opens up new possibilities for cuproptosis-related therapy for CCA. The cuproptosis key gene GCSH has been preliminarily confirmed as a reliable therapeutic target or prognostic marker for CCA patients.
Keywords: Cholangiocarcinomas, Cuproptosis, Prognostic model, GCSH
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