Gene expression and prognosis of x-ray repair cross-complementing family members in non-small cell lung cancer

ABSTRACT

The X-ray repair cross-complementing gene (XRCC) family participates in DNA damage repair and its dysregulation is associated with the development and progression of a variety of cancers. However, XRCCs have not been systematically studied in non-small cell lung cancer (NSCLC). Using The Cancer Genome Atlas (TCGA) and Oncomine databases, we compared the expression levels of XRCCs between NSCLC and normal tissues and performed survival analysis using the data from TCGA. The correlations of XRCCs with the clinical parameters were then analyzed using UCSC Xena. Genetic alterations in XRCCs in NSCLC and their effects on the prognosis of patients were presented using cBioPortal. SurvivalMeth was used to explore the differentially methylated sites associated with NSCLC and their effect on prognosis. Next, the immunological correlations of XRCCs expression level were analyzed using TIMER 2.0. Finally, GeneMANIA was used to visualize and analyze the functionally relevant genes, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional and pathway enrichment analyses of prognostic genes. Our results revealed that XRCCs were overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Univariate and multivariate Cox analyses showed that XRCC4/5/6 were independent risk factors for LUAD. Additionally, genetic alterations, methylation, and immune cell infiltration demonstrated an association between XRCC4/5/6 and poor prognosis in LUAD. Finally, the KEGG-enriched and non-homologous end-joining (NHEJ) pathways were shown to be associated with XRCC4/5/6. In conclusion, our study demonstrated that XRCC4/5/6 could be used as diagnostic and prognostic biomarkers for LUAD.

KEYWORDS:

• X-ray repair cross-complementing (xrcc) gene family
• lung adenocarcinoma (luad)
• lung squamous carcinoma (lusc)
• prognosis
• bioinformatics

Acknowledgements

We thank TCGA, Oncomine, UCSC Xena, cBioPortal and other open databases for providing platforms and contributors for uploading meaningful datasets.

Data Availability

This study analyzed publicly available online datasets. TCGA:https://cancergenome. nih.gov/;UCSC Xena:https://xenabrowser.net/;Oncomine: https://www.oncomine. org/resource/login.html;cBioPortal:http://www.cbioportal.org/;SuvivalMeth:http://bio-bigdata.hrbmu.edu.cn/survivalmeth/; GeneMANIA:http://www.genemania.org;TIMER2.0: http://timer.cistrome.org/; CellMiner: https://discover.nci.nih.gov/cellminer/home.do

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author Contributions

Yongfei Fan and Zhaojia Gao designed the subject and wrote the manuscript. Xinwei Li contributed to the data compilation. Shuzhang Wei contributed to the literature search, improving the project proposal and revising the manuscript. All authors reviewed the manuscript and approved the manuscript for publication.

Abbreviations

XRCC: X-ray repair cross-complementing; NSCLC: non-small cell lung cancer; LUAD: lung adenocarcinoma; LUSC: lung squamous carcinoma; TCGA: the Cancer Genome Atlas; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: Biological Process; NHEJ: the Non-homologous end-joining; TIMER: the Tumor Immune Estimation Resource; UCSC: the University of California Santa Cruz; OS: Overall Survival; DFS: Disease-Free Survival; BP: biological processes; CC: cellular components; MF: molecular functions

Additional information

Funding

This work is supported by the following funds:1. ‘333 Project’ of Jiangsu Province (Grant number: BRA2020157)2. ‘Six One Project,’ Research Projects of High-level Medical Personnel of Jiangsu Province (Grant number: LGY2019025)3. High-level Talent Selection and Training Project of the 16th Batch of ‘Six Talent Peak’ in Jiangsu Province (Grant number: WSN-245)4. Medical Scientific Research Foundation of Jiangsu Commission of Health (Grant number: H2018083)5. Jiangsu Provincial Medical Youth Talent (Jiangsu Health Scientific Education 2017 no.3)6. 333 High-Level Talent Training Project (Grant number: 2016, III-0719)7. High-Level Medical Talents Training Project (Grant number: 2016CZBJ042)