Research Paper Volume 16, Issue 1 pp 872—910
XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis
- 1 Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- 2 Medical Clinical Laboratory, Yibin Hospital of T.C.M, Yibin, China
- 3 Queen Mary College, Medical School of Nanchang University, Nanchang, China
- 4 Clinical Medical College, Southwest Medical University, Luzhou, China
- 5 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
- 6 Department of Specialty Medicine, Ohio University, Athens, OH 45701, USA
Received: June 26, 2023 Accepted: December 1, 2023 Published: January 12, 2024
https://doi.org/10.18632/aging.205426How to Cite
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking. To address this knowledge gap, we conducted a systematic investigation employing bioinformatics techniques across 33 cancer types. Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases. Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, we observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, our findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy.
Abbreviations
ACC: Adrenocortical carcinoma; AML: Acute myeloid leukemia; BER: Base excision repair; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; c-BioPortal: cBio Cancer Genomics Portal; CCLE: Cancer Cell Line Encyclopedia; CHOL: Cholangiocarcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CK2: Casein kinase 2; CNV: Copy number variation; COAD: Colon adenocarcinoma; DEGs: Differential expression genes; DFS: Disease-free survival; DSS: Disease-specific survival; ESCA: Esophageal carcinoma; FC: Fold-change; GDC: Genomic Data Commons; GBM: Glioblastoma multiforme; GSEA: Gene Set Enrichment Analysis; GTEx: Genotype Tissue Expression; HNSC: Head and neck adenocarcinoma; HPA: Human Protein Atlas; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LGG: Lower grade glioma; Lig-III: Ligase IIIα; LIHC: Liver hepatocellular carcinoma; LUSC: Lung squamous cell carcinoma; LUAD: Lung adenocarcinoma; MESO: Mesothelioma; MMEJ: Microhomology-mediated end joining; MSI: Microsatellite instability; OS: Overall survival; OSCC: Oral squamous cell carcinoma; PFS: Progression-free survival; READ: Rectum adenocarcinoma; ROC: Receiver operating characteristic; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; SSBR: Single-strand break repair; STAD: Stomach adenocarcinoma; STRING: Search Tool for the Retrieval of Interacting Genes/Proteins; TAM: Tumor-associated macrophages; TGCT: Testicular germ cell tumor; THYM: Thymoma; TMB: Tumor Mutation Burden; TME: Tumor microenvironment; TPM: Transcripts per million reads; PCPG: Pheochromocytoma and paraganglioma; PD-L1: Programmed death ligand 1; PD-1: Programmed cell death 1; PPI: Protein-Protein Interaction; PRAD: Prostate adenocarcinoma; UCS: Uterine carcinosarcoma; XRCC1: X-ray repair cross-complementation group 1.