Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer
Abstract 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Bioinformatics |
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| Online Access: | https://doi.org/10.1186/s12859-023-05165-8 |
| _version_ | 1811165718928949248 |
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| author | Yang Yu Yanyan Sun Zhaoxian Li Jiang Li Dazhi Tian |
| author_facet | Yang Yu Yanyan Sun Zhaoxian Li Jiang Li Dazhi Tian |
| author_sort | Yang Yu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T15:41:13Z |
| format | Article |
| id | doaj.art-a8771f6077f14d3ea7da93e1e8064510 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-10T15:41:13Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-a8771f6077f14d3ea7da93e1e80645102023-02-12T12:24:25ZengBMCBMC Bioinformatics1471-21052023-02-0124111710.1186/s12859-023-05165-8Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancerYang Yu0Yanyan Sun1Zhaoxian Li2Jiang Li3Dazhi Tian4Organ Transplant Center, Tianjin First Central Hospital, Nankai UniversityOrgan Transplant Center, Tianjin First Central Hospital, Nankai UniversityOrgan Transplant Center, Tianjin First Central Hospital, Nankai UniversityOrgan Transplant Center, Tianjin First Central Hospital, Nankai UniversityOrgan Transplant Center, Tianjin First Central Hospital, Nankai UniversityAbstract 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.https://doi.org/10.1186/s12859-023-05165-8XRCC4Pan-cancerPrognosisImmuneDrug sensitivity |
| spellingShingle | Yang Yu Yanyan Sun Zhaoxian Li Jiang Li Dazhi Tian Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer BMC Bioinformatics XRCC4 Pan-cancer Prognosis Immune Drug sensitivity |
| title | Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer |
| title_full | Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer |
| title_fullStr | Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer |
| title_full_unstemmed | Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer |
| title_short | Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer |
| title_sort | systematic analysis identifies xrcc4 as a potential immunological and prognostic biomarker associated with pan cancer |
| topic | XRCC4 Pan-cancer Prognosis Immune Drug sensitivity |
| url | https://doi.org/10.1186/s12859-023-05165-8 |
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