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Published on: May 17, 2019
Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer
Yang Yu1, Yanyan Sun1, Zhaoxian Li1,2
1Organ Transplant Center, Tianjin First Central Hospital, Nankai University, Tianjin, 300190, China.
Background:
XRCC4 is a NHEJ factor identified recently that plays a vital role in repairing DNA double-stranded breaks. Studies have reported the associations between abnormal expression of XRCC4 and tumor susceptibility and radiosensitivity, but the potential biological mechanisms by which XRCC4 exerts effects on tumorigenesis are not fully understood. This study aimed to systematically investigate the role of XRCC4 across cancer types.
Methods:
The TIMER, GTEX and Xiantao Academic database were used to interpret the expression of XRCC4. Genomic alterations and protein expression in human organic and tumor tissues were applied in cBioPortal and the Human Protein Atlas databases. Correlations between XRCC4 expression and immune and molecular subtypes were analyzed by using the TISIDB database. Protein-protein interactions, GO and KEGG enrichment were also applied for XRCC4-related genes. The TIMER and the Tumor Immune Single Cell Hub (TISCH) online databases were used to explore the relationship between XRCC4 and tumor immune microenvironment. Drug sensitivity information was acquired from the CellMiner database to analyze the effect of XRCC4 on sensitivity analysis.
Results:
The XRCC4 expression was significantly upregulated in 15 tumor types and downregulated in two tumor types compared with the normal tissues, most of which were validated by the results of Xiantao academic platform. XRCC4 was expressed at intermediate level in malignant cells. The XRCC4 expression was related to the molecular and immune subtypes of human cancers, and the survival outcome of 11 types of cancers, including KIRC, STAD and LIHC. The main type of frequent genetic alteration is amplification. Strong correlations were also found between XRCC4 and immune checkpoint genes in 33 human cancers. Furthermore, the abnormal expression of XRCC4 was related to immune cell infiltration and drug sensitivity. Enrichment analysis showed that XRCC4 was significantly correlated with DNA damage response.
Conclusions:
This comprehensive pan-cancer analysis suggested that XRCC4 may play a vital role in the prognosis and immunotherapy response in cancer patients, and it is a promising therapy target in the future.
Insights
The DNA repair protein XRCC4 is frequently altered in many cancers, impacting patient prognosis and immune response. Its role in tumorigenesis suggests XRCC4 as a potential therapeutic target for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- XRCC4 is a key non-homologous end joining (NHEJ) factor involved in DNA double-strand break repair.
- Abnormal XRCC4 expression is linked to tumor susceptibility and radiosensitivity, but its precise role in tumorigenesis requires further elucidation.
Purpose of the Study:
- To systematically investigate the role of XRCC4 across various cancer types.
- To explore the association of XRCC4 with cancer subtypes, immune microenvironment, and therapeutic sensitivity.
Main Methods:
- Utilized TIMER, GTEX, Xiantao Academic, cBioPortal, Human Protein Atlas, and TISIDB databases for expression and genomic alteration analysis.
- Analyzed XRCC4-related gene interactions, GO/KEGG enrichment, and its relationship with tumor immune microenvironment and drug sensitivity using TISCH and CellMiner.
Main Results:
- XRCC4 expression was significantly altered in 15/17 tumor types, with amplification being the main genetic alteration.
- XRCC4 expression correlated with molecular/immune subtypes, survival outcomes in 11 cancer types, and immune checkpoint genes.
- Abnormal XRCC4 expression was associated with immune cell infiltration, drug sensitivity, and DNA damage response pathways.
Conclusions:
- XRCC4 plays a significant role in cancer prognosis and immunotherapy response.
- XRCC4 represents a promising therapeutic target for future cancer treatments.
