Abstract
Background: Lung adenocarcinoma (LUAD) is a common malignancy with a poor prognosis due to the lack of predictive markers. DNA damage repair (DDR)-related genes are closely related to cancer progression and treatment.
Introduction: To identify a reliable DDR-related gene signature as an independent predictor of LUAD.
Methods: DDR-related genes were obtained using combined analysis of TCGA-LUAD data and literature information, followed by the identification of DDR-related prognostic genes. The DDRrelated molecular subtypes were then screened, followed by Kaplan-Meier analysis, feature gene identification, and pathway enrichment analysis of each subtype. Moreover, Cox and LASSO regression analyses were performed for the feature genes of each subtype to construct a prognostic model. The clinical utility of the prognostic model was confirmed using the validation dataset GSE72094 and nomogram analysis.
Results: Eight DDR-related prognostic genes were identified from 31 DDR-related genes. Using consensus cluster analysis, three molecular subtypes were screened. Cluster2 had the best prognosis, while cluster3 had the worst. Compared to cluster2, clusters 1 and 3 consisted of more stage3 - 4, T2-T4, male, and older samples. The feature genes of clusters1, 2, and 3 were mainly enriched in the cell cycle, arachidonic acid metabolism, and ribosomes. Furthermore, a 15-feature gene signature was identified for improving the prognosis of LUAD patients.
Conclusion: The 15 DDR-related feature gene signature is an independent and powerful prognostic biomarker for LUAD that may improve risk classification and provide supplementary information for a more accurate evaluation and personalized treatment.
Keywords: Adenocarcinoma of lung, DNA repair, prognosis, transcriptome, DDR-related gene, malignancy.
Graphical Abstract
[PMID: 11782381]
[http://dx.doi.org/10.1002/cncr.32802] [PMID: 32162336]
[http://dx.doi.org/10.1016/j.trsl.2015.08.001] [PMID: 26318634]
[http://dx.doi.org/10.1007/978-3-319-24223-1_1] [PMID: 26667336]
[http://dx.doi.org/10.1186/s12885-019-6462-y] [PMID: 31987030]
[http://dx.doi.org/10.3399/bjgp17X690917] [PMID: 28483820]
[http://dx.doi.org/10.1038/nature25183] [PMID: 29364287]
[http://dx.doi.org/10.1016/j.pharmthera.2016.02.003] [PMID: 26896565]
[http://dx.doi.org/10.1038/nrm.2017.56] [PMID: 28655905]
[http://dx.doi.org/10.3389/fonc.2018.00015] [PMID: 29459886]
[http://dx.doi.org/10.1634/theoncologist.2019-0034] [PMID: 31040255]
[http://dx.doi.org/10.1186/s40425-019-0619-8] [PMID: 31174611]
[http://dx.doi.org/10.1016/j.celrep.2018.03.076] [PMID: 29617664]
[http://dx.doi.org/10.1038/s41587-020-0546-8] [PMID: 32444850]
[PMID: 23193258]
[http://dx.doi.org/10.1093/bioinformatics/btq170] [PMID: 20427518]
[http://dx.doi.org/10.1186/1471-2105-14-7] [PMID: 23323831]
[http://dx.doi.org/10.1093/bioinformatics/btr260] [PMID: 21546393]
[http://dx.doi.org/10.1038/onc.2016.303] [PMID: 27775076]
[http://dx.doi.org/10.1093/bioinformatics/bts251] [PMID: 22543366]
[PMID: 21807066]
[http://dx.doi.org/10.3892/or.2017.5724] [PMID: 28627709]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-1027] [PMID: 20802015]
[http://dx.doi.org/10.3390/medicina56020048] [PMID: 31973027]
[http://dx.doi.org/10.1002/cncr.29041] [PMID: 25224030]
[http://dx.doi.org/10.1016/j.molcel.2018.11.003] [PMID: 30554948]
[http://dx.doi.org/10.1083/jcb.201703144] [PMID: 28912125]
[http://dx.doi.org/10.3390/cancers11101548] [PMID: 31614901]
[http://dx.doi.org/10.1371/journal.pgen.1002786] [PMID: 22792074]
[http://dx.doi.org/10.2217/fon.10.191] [PMID: 21345144]
[http://dx.doi.org/10.1016/j.tig.2017.11.006] [PMID: 29254745]
[http://dx.doi.org/10.1158/2159-8290.CD-17-0151] [PMID: 28572459]
[http://dx.doi.org/10.1148/rg.305095166] [PMID: 20833843]
[http://dx.doi.org/10.1038/s41598-020-64068-3] [PMID: 32341400]
[http://dx.doi.org/10.1186/s13073-016-0289-9] [PMID: 27036109]
[http://dx.doi.org/10.18632/oncotarget.7710] [PMID: 26934654]
[http://dx.doi.org/10.1186/s12935-020-01428-z] [PMID: 32699528]
[http://dx.doi.org/10.3892/ol.2018.8192] [PMID: 29725427]
[http://dx.doi.org/10.1186/s13045-019-0738-1] [PMID: 31151482]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2661] [PMID: 15930332]
[http://dx.doi.org/10.1093/carcin/bgl023] [PMID: 16704987]
[http://dx.doi.org/10.1038/s41389-018-0044-8] [PMID: 29674660]
[http://dx.doi.org/10.1038/s41598-017-02990-9] [PMID: 28600503]
[http://dx.doi.org/10.1200/JGO.2019.5.suppl.53]
[http://dx.doi.org/10.2147/CMAR.S193793] [PMID: 31114363]
[http://dx.doi.org/10.3389/fonc.2020.00180] [PMID: 32195172]
[http://dx.doi.org/10.3390/cancers11030320] [PMID: 30845770]
[http://dx.doi.org/10.1126/science.aan2507] [PMID: 28818916]
[http://dx.doi.org/10.5772/intechopen.87963]
[http://dx.doi.org/10.1038/cddis.2017.13] [PMID: 28151475]
[http://dx.doi.org/10.18632/oncotarget.3107] [PMID: 25762627]
[http://dx.doi.org/10.1016/j.ebiom.2015.09.012] [PMID: 26870806]
[http://dx.doi.org/10.3892/ol.2020.11819] [PMID: 32782587]
[http://dx.doi.org/10.1038/s41523-020-0170-2] [PMID: 32656317]