Research Paper Volume 15, Issue 10 pp 4269—4287
Systematic pan-cancer analysis identifies cuproptosis-related gene DLAT as an immunological and prognostic biomarker
- 1 Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China
- 2 Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450000, China
- 3 Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450000, China
- 4 Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China
Received: October 29, 2022 Accepted: May 3, 2023 Published: May 17, 2023
https://doi.org/10.18632/aging.204728How to Cite
Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Lipoylated dihydrolipoamide S-acetyltransferase (DLAT), the component E2 of the multi-enzyme pyruvate dehydrogenase complex, is one of the key molecules of cuproptosis. However, the prognostic value and immunological role of DLAT in pan-cancer are still unclear. Using a series of bioinformatics approaches, we studied combined data from different databases, including the Cancer Genome Atlas, Genotype Tissue-Expression, the Cancer Cell Line Encyclopedia, Human Protein Atlas, and cBioPortal to investigate the role of DLAT expression in prognosis and tumor immunity response. We also reveal the potential correlations between DLAT expression and gene alterations, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that DLAT displays abnormal expression within most malignant tumors. Through gene set enrichment analysis (GSEA), we found that DLAT was significantly associated with immune-related pathways. Further, the expression of DLAT was also confirmed to be correlated with the tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophages (TAMs). In addition, we found that DLAT is co-expressed with genes encoding major histocompatibility complex (MHC), immunostimulators, immune inhibitors, chemokines, and chemokine receptors. Meanwhile, we demonstrate that DLAT expression is correlated with TMB in 10 cancers and MSI in 11 cancers. Our study reveals that DLAT plays an essential role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.
Abbreviations
TCGA: The Cancer Genome Atlas; TME: tumor microenvironment; ICIs: immune checkpoint inhibitors; DLAT: lipoylated dihydrolipoamide S-acetyltransferase; GTEx: Genotype Tissue-Expression; CCLE: Cancer Cell Line Encyclopedia; HPA: Human Protein Atlas; CNV: copy number variation; TMB: tumor mutational burden; MSI: microsatellite instability; GSEA: gene set enrichment analysis; IHC: immunohistochemistry; OS: overall survival; DSS: disease-specific survival; DFI: disease-free interval; PFI: progression-free interval; KM: Kaplan-Meier; HR: hazard ratio; MHC: major histocompatibility complex; BCR: B Cell Receptor; TAMs: tumor-associated macrophages; ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; COADREAD: colon adenocarcinoma/rectum adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; GBMLGG: Glioma; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIPAN: pan-kidney cohort; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukemia; LGG: brain lower grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; SKCM-M: metastatic skin cutaneous melanoma; SKCM-P: primary skin cutaneous melanoma; STAD: stomach adenocarcinoma; STES: stomach and esophageal carcinoma; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; UVM: uveal melanoma.