Comprehensive analysis of the cuproptosis-related gene DLD across cancers: A potential prognostic and immunotherapeutic target

Weiguang Yang; Qiang Guo; Haiyang Wu; Linjian Tong; Jian Xiao; Yulin Wang; Rui Liu; Lixia Xu; Hua Yan; Zhiming Sun

doi:10.3389/fphar.2023.1111462

Comprehensive analysis of the cuproptosis-related gene DLD across cancers: A potential prognostic and immunotherapeutic target

Front Pharmacol. 2023 Apr 3:14:1111462. doi: 10.3389/fphar.2023.1111462. eCollection 2023.

Authors

Weiguang Yang^{1

2}, Qiang Guo^{1

3}, Haiyang Wu^{1

2

4}, Linjian Tong^{1

2}, Jian Xiao^{1

2}, Yulin Wang^{1

2}, Rui Liu^{1

2}, Lixia Xu⁵, Hua Yan^{1

5}, Zhiming Sun^{1

6}

Affiliations

¹ Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China.
² Department of Graduate School, Tianjin Medical University, Tianjin, China.
³ Department of Orthopaedics, Baodi Clinical College of Tianjin Medical University, Tianjin, China.
⁴ Duke Molecular Physiology Institute, Duke University School of Medicine, Duke University, Durham, NC, United States.
⁵ Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, China.
⁶ Department of Orthopaedics, Tianjin Huanhu Hospital, Tianjin, China.

Abstract

DLD is a key gene involved in "cuproptosis," but its roles in tumor progression and immunity remain unclear. Exploring the potential mechanisms and biological roles of DLD may provide new insights for therapeutic strategies for tumors. In the present study, we analyzed the role of DLD in a variety of tumors by using several bioinformatic tools. The results showed that compared with normal tissues, tumor tissues representing multiple cancers showed significant differential expression of DLD. High DLD expression was associated with a good prognosis in BRCA, KICH, and LUAD. Conversely, high expression levels of DLD were detrimental to patient prognosis in many other tumors, such as COAD, KIRC, and KIRP. In addition, the associations of DLD with infiltrating immune cells, genetic alterations and methylation levels across cancers were assessed. Aberrant expression of DLD was positively correlated with most infiltrating immune cells, especially neutrophils. The DLD methylation level was significantly decreased in COAD, LIHC, and LUSC but significantly increased in BRCA. DLD had the highest mutation rate (6.04%) in ESCA. In LUSC, patients with genetic alterations in DLD showed a poorer prognosis. At the single-cell level, the roles of DLD in regulating cancer-associated biological functions, such as metastasis, inflammation, and differentiation, were explored. Afterward, we further investigated whether several disease-associated genes could be correlated with DLD. GO enrichment analysis indicated that DLD-related genes were mainly associated with mitochondria-related cellular components, aerobic respiration and the tricarboxylic acid cycle. Finally, the correlations between DLD expression and immunomodulatory genes, immune checkpoints, and sensitivity to some antitumor drugs were investigated. It is worth noting that DLD expression was positively correlated with immune checkpoint genes and immunomodulatory genes in most cancers. In conclusion, this study comprehensively analyzed the differential expression, prognostic value and immune cell infiltration-related function of DLD across cancers. Our results suggest that DLD has great potential to serve as a candidate marker for pancancer prognosis and immunotherapy and may provide a new direction for cancer treatment development.

Keywords: bioinformatics analysis; cuproptosis; dld; immune cell infiltration; pan-cancer; prognosis.

Grants and funding

This work was supported by the Tianjin Municipal Health Bureau (grant number 14KG115) and the Key Program of the Natural Science Foundation of Tianjin (grant number 20JCZDJC00730).