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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Detection of Stage-wise Biomarkers in Lung Adenocarcinoma Using Multiplex Analysis

Author(s): Athira K*, Sunil Kumar P V, Manju M and Gopakumar G

Volume 18, Issue 6, 2023

Published on: 18 April, 2023

Page: [472 - 483] Pages: 12

DOI: 10.2174/1574893618666230228112411

Price: $65

Abstract

Introduction: Lung cancer is the leading cancer in terms of morbidity and mortality rate. Its prevalence has been steadily increasing over the world in recent years. An integrated study is unavoidable to analyse the cascading interrelationships between molecular cell components at multiple levels resulting in hidden biological events in cancer.

Methods: Multiplex network modeling is a unique methodology that could be used as an integrative method for dealing with diverse interactions. Here, we have employed a multiplex framework to model the lung adenocarcinoma (LUAD) network by incorporating co-expression correlations, methylation relations, and protein physical binding interactions as network layers. Hub nodes identified from the multiplex network utilizing centrality measures, including degree, eigenvector, and random walk with a random jump technique, are considered as biomarker genes. These stage-wise biomarker genes identified for LUAD are investigated using GO enrichment analysis, pathway analysis, and literature evidence to determine their significance in tumor progression.

Results: The study has identified a set of stage-specific biomarkers in LUAD. The 31 genes identified from the results of multiple centrality analysis can be targeted as novel diagnostic biomarkers in LUAD. Multiple signaling pathways identified here may be considered as potential targets of interest.

Conclusion: Based on the analysis results, patients may be identified by their stage of cancer progression, which can aid in treatment decision-making.

[1]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin 2021; 71(1): 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[2]
Daugaard I, Dominguez D, Kjeldsen TE, et al. Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma. Sci Rep 2016; 6(1): 35807.
[http://dx.doi.org/10.1038/srep35807] [PMID: 28442746]
[3]
Travis WD. Pathology of lung cancer. Clin Chest Med 2011; 32(4): 669-92.
[http://dx.doi.org/10.1016/j.ccm.2011.08.005] [PMID: 22054879]
[4]
Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
[http://dx.doi.org/10.1038/35057062] [PMID: 11237011]
[5]
Network CGAR. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014; 511(7511): 543-50.
[http://dx.doi.org/10.1038/nature13385] [PMID: 25079552]
[6]
Ramazzotti D, Lal A, Wang B, Batzoglou S, Sidow A. Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival. Nat Commun 2018; 9(1): 4453.
[http://dx.doi.org/10.1038/s41467-018-06921-8] [PMID: 29317637]
[7]
Chaudhary K, Poirion OB, Lu L, Garmire LX. Deep learning–based multi-omics integration robustly predicts survival in liver cancer. Clin Cancer Res 2018; 24(6): 1248-59.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0853] [PMID: 28982688]
[8]
Calvayrac O, Pradines A, Pons E, Mazières J, Guibert N. Molecular biomarkers for lung adenocarcinoma. Eur Respir J 2017; 49(4): 1601734.
[http://dx.doi.org/10.1183/13993003.01734-2016] [PMID: 28381431]
[9]
Zhang B, Wang R, Li K, et al. An immune-related lncRNA expression profile to improve prognosis prediction for lung adenocarcinoma: From bioinformatics to clinical word. Front Oncol 2021; 11: 671341.
[http://dx.doi.org/10.3389/fonc.2021.671341] [PMID: 33968781]
[10]
Zhou Y, Xu B, Zhou Y, Liu J, Zheng X, Liu Y. Identification of key genes with differential correlations in lung adenocarcinoma. Front Cell Dev Biol 2021; 9: 915.
[11]
Jagga Z, Gupta D. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms. BMC proceedings 8 (Supp 6): 1-7.
[http://dx.doi.org/10.1186/1753-6561-8-S6-S2]
[12]
Singh NP, Bapi RS, Vinod PK. Machine learning models to predict the progression from early to late stages of papillary renal cell carcinoma. Comput Biol Med 2018; 100: 92-9.
[http://dx.doi.org/10.1016/j.compbiomed.2018.06.030] [PMID: 29990647]
[13]
Hamzeh O, Alkhateeb A, Zheng JZ, et al. A hierarchical machine learning model to discover gleason grade-specific biomarkers in prostate cancer. Diagnostics 2019; 9(4): 219.
[http://dx.doi.org/10.3390/diagnostics9040219] [PMID: 31835700]
[14]
Goebel C, Louden CL, McKenna R Jr, Onugha O, Wachtel A, Long T. Diagnosis of non-small cell lung cancer for early stage asymptomatic patients. Cancer Genom Proteomics 2019; 16(4): 229-44.
[http://dx.doi.org/10.21873/cgp.20128] [PMID: 31243104]
[15]
Kivelä M, Arenas A, Barthelemy M, Gleeson JP, Moreno Y, Porter MA. Multilayer networks. J Complex Netw 2014; 2(3): 203-71.
[http://dx.doi.org/10.1093/comnet/cnu016]
[16]
Colaprico A, Silva TC, Olsen C, et al. TCGAbiolinks: An R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res 2016; 44(8): e71-1.
[http://dx.doi.org/10.1093/nar/gkv1507] [PMID: 26704973]
[17]
Price EM, Cotton AM, Lam LL, et al. Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium human methylation 450 bead chip array. Epigenet Chromatin 2013; 6(1): 4.
[http://dx.doi.org/10.1186/1756-8935-6-4] [PMID: 23289424]
[18]
Naeem H, Wong NC, Chatterton Z, et al. Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array. BMC Genom 2014; 15(1): 51.
[http://dx.doi.org/10.1186/1471-2164-15-51] [PMID: 24447442]
[19]
Moen EL, Litwin E, Arnovitz S, et al. Characterization of CpG sites that escape methylation on the inactive human X-chromosome. Epigenetics 2015; 10(9): 810-8.
[http://dx.doi.org/10.1080/15592294.2015.1069461] [PMID: 26178744]
[20]
Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43(7): e47-7.
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[21]
Wang F, Zhang S, Liu H, et al. CellMethy: Identification of a focal concordantly methylated pattern of CpGs revealed wide differences between normal and cancer tissues. Sci Rep 2015; 5(1): 18037.
[http://dx.doi.org/10.1038/srep18037]
[22]
Guan Y, Gorenshteyn D, Burmeister M, et al. Tissue-specific functional networks for prioritizing phenotype and disease genes. PLOS Comput Biol 2012; 8(9): e1002694.
[http://dx.doi.org/10.1371/journal.pcbi.1002694] [PMID: 23028291]
[23]
Magger O, Waldman YY, Ruppin E, Sharan R. Enhancing the prioritization of disease-causing genes through tissue specific protein interaction networks. PLOS Comput Biol 2012; 8(9): e1002690.
[http://dx.doi.org/10.1371/journal.pcbi.1002690] [PMID: 23028288]
[24]
Ostrow SL, Barshir R, DeGregori J, Yeger-Lotem E, Hershberg R. Cancer evolution is associated with pervasive positive selection on globally expressed genes. PLoS Genet 2014; 10(3): e1004239.
[http://dx.doi.org/10.1371/journal.pgen.1004239] [PMID: 24603726]
[25]
Zitnik M, Leskovec J. Predicting multicellular function through multi-layer tissue networks. Bioinformatics 2017; 33(14): i190-8.
[http://dx.doi.org/10.1093/bioinformatics/btx252] [PMID: 28881986]
[26]
De Domenico M, Solé-Ribalta A, Cozzo E, et al. Mathematical formulation of multilayer networks. Phys Rev X 2013; 3(4): 041022.
[http://dx.doi.org/10.1103/PhysRevX.3.041022]
[27]
Athira K, Gopakumar G. An integrated method for identifying essential proteins from multiplex network model of protein–protein interactions. J Bioinform Comput Biol 2020; 18(4): 2050020-0.
[http://dx.doi.org/10.1142/S0219720020500201] [PMID: 32795133]
[28]
Pan JY, Yang HJ, Faloutsos C, Duygulu P. Automatic mul- timedia cross-modal correlation discovery. Proceedings of the tenth ACM SIGKDD international conference on knowledge discovery and data mining. Seattle, USA. New York: Association for Computing Machinery 2004; pp. 653-8.
[29]
Valdeolivas A, Tichit L, Navarro C, et al. Random walk with restart on multiplex and heterogeneous biological networks. Bioinformatics 2019; 35(3): 497-505.
[http://dx.doi.org/10.1093/bioinformatics/bty637] [PMID: 30020411]
[30]
De Domenico M, Solé-Ribalta A, Gómez S, Arenas A. Navigability of interconnected networks under random failures. Proc Natl Acad Sci USA 2014; 111(23): 8351-6.
[http://dx.doi.org/10.1073/pnas.1318469111] [PMID: 24912174]
[31]
Fabregat A, Jupe S, Matthews L, et al. The reactome pathway knowledge- base. Nucleic Acids Res 2018; 46(D1): D649-55.
[http://dx.doi.org/10.1093/nar/gkx1132] [PMID: 29145629]
[32]
Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: A comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 2016; 44(W1): W90-7.
[http://dx.doi.org/10.1093/nar/gkw377] [PMID: 27141961]
[33]
Bao X, Shi R, Zhao T, Wang Y. Immune landscape and a novel immunotherapy-related gene signature associated with clinical outcome in early-stage lung adenocarcinoma. J Mol Med 2020; 98(6): 805-18.
[http://dx.doi.org/10.1007/s00109-020-01908-9] [PMID: 32333046]
[34]
Sojka DR, Gogler-Pigłowska A, Vydra N, et al. Functional redundancy of HSPA1, HSPA2 and other HSPA proteins in non-small cell lung carcinoma (NSCLC); An implication for NSCLC treatment. Sci Rep 2019; 9(1): 14394.
[http://dx.doi.org/10.1038/s41598-019-50840-7] [PMID: 31591429]
[35]
Huang ZC, Li H, Sun ZQ, et al. Distinct prognostic roles of HSPB1 expression in non-small cell lung cancer. Neoplasma 2018; 65(1): 161-6.
[http://dx.doi.org/10.4149/neo_2018_102] [PMID: 29017331]
[36]
Wang L, Zhao H, Zhang L, Luo H, Chen Q, Zuo X. HSP90AA1, ADRB2, TBL1XR1 and HSPB1 are chronic obstructive pulmonary disease related genes that facilitate squamous cell lung cancer progression. Oncol Lett 2020; 19(3): 2115-22.
[http://dx.doi.org/10.3892/ol.2020.11318] [PMID: 32194709]
[37]
Hsu T-I, Wang M-C, Chen S-Y, et al. Sp1 expression regulates lung tumor progression. Oncogene 2012; 31(35): 3973-88.
[http://dx.doi.org/10.1038/onc.2011.568] [PMID: 22158040]
[38]
Lou Y, Xu J, Zhang Y, et al. Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis. Cell Death Dis 2021; 12(2): 170.
[http://dx.doi.org/10.1038/s41419-021-03439-8] [PMID: 33568630]
[39]
Wang N, Wang W, Mao W, Kuerbantayi N, Jia N, Chen Y. RBBP4 enhances platinum chemo resistance in lung adenocarcinoma. BioMed Res Int 2021; 2021: 6905985.
[http://dx.doi.org/10.1155/2021/6905985]
[40]
Mogi A, Kuwano H. TP53 mutations in nonsmall cell lung cancer. J Biomed Biotechnol 2011; 2011: 583929.
[http://dx.doi.org/10.1155/2011/583929]
[41]
Dono A, Takayasu T, Yan Y, et al. Differences in genomic alterations between brain metastases and primary tumors. Neurosurgery 2021; 88(3): 592-602.
[http://dx.doi.org/10.1093/neuros/nyaa471] [PMID: 33369669]
[42]
Carrà G, Ermondi G, Riganti C, et al. IκBα targeting promotes oxidative stress-dependent cell death. J Exp Clin Cancer Res 2021; 40(1): 136.
[http://dx.doi.org/10.1186/s13046-021-01921-x] [PMID: 33390177]
[43]
Lin Y, Zhang J, Cai J, et al. Systematic analysis of gene expression alteration and co- expression network of eukaryotic initiation factor 4A-3 in cancer. J Cancer 2018; 9(24): 4568-77.
[http://dx.doi.org/10.7150/jca.27655] [PMID: 30588240]
[44]
Chen X, Xie D, Zhao Q, You ZH. MicroRNAs and complex diseases: From experimental results to computational models. Brief Bioinform 2019; 20(2): 515-39.
[http://dx.doi.org/10.1093/bib/bbx130] [PMID: 29045685]
[45]
Wang CC, Han CD, Zhao Q, Chen X. Circular RNAs and complex diseases: From experimental results to computational models. Brief Bioinform 2021; 22(6): bbab286.
[http://dx.doi.org/10.1093/bib/bbab286] [PMID: 34329377]
[46]
Chen X, Li TH, Zhao Y, Wang CC, Zhu CC. Deep-belief network for predicting potential miRNA-disease associations. Brief Bioinform 2021; 22(3): bbaa186.
[http://dx.doi.org/10.1093/bib/bbaa186] [PMID: 34020550]
[47]
Chen X, Sun LG, Zhao Y. NCMCMDA: miRNA–disease association prediction through neighborhood constraint matrix completion. Brief Bioinform 2021; 22(1): 485-96.
[http://dx.doi.org/10.1093/bib/bbz159] [PMID: 31927572]

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