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Clinical and Translational Oncology

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01-10-2020 | Lung Cancer | Research Article

Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer

Authors: M. Arroyo, R. Larrosa, J. Gómez-Maldonado, M. Á. Cobo, M. G. Claros, R. Bautista

Published in: Clinical and Translational Oncology | Issue 10/2020

Abstract

Overview

Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment.

Material and methods

High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs).

Results

A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities.

Conclusions

This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.

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Afink G, Kulik W, Overmars H, de Randamie J, Veenboer T, van Cruchten A, Craen M, Ris-Stalpers C. Molecular characterization of iodotyrosine dehalogenase deficiency in patients with hypothyroidism. J Clin Endocrinol Metab. 2008;93(12):4894–901. https://doi.org/10.1210/jc.2008-0865.CrossRefPubMed

Arroyo M, Bautista R, Larrosa R, de la Cruz JL, Cobo MA, Claros MG. Potencial uso biomarcador de los retrotransposones en el adenocarcinoma de pulmón. Revista Española de Patología Torácica. 2018;30(4):224–30.

Arroyo M, Bautista R, Larrosa R, Cobo MÁ, Claros MG. Biomarker potential of repetitive-element transcriptome in lung cancer. PeerJ. 2019;7:e8277. https://doi.org/10.7717/peerj.8277.CrossRefPubMedPubMedCentral

Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW. Translating rna sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016;17(5):257–71. https://doi.org/10.1038/nrg.2016.10.CrossRefPubMedPubMedCentral

Cenni B, Gutmann S, Gottar-Guillier M. Bmx and its role in inflammation, cardiovascular disease, and cancer. Int Rev Immunol. 2012;31(2):166–73. https://doi.org/10.3109/08830185.2012.663838.CrossRefPubMed

Chahal M, Pleasance E, Grewal J, Zhao E, Ng T, Chapman E, Jones MR, Shen Y, Mungall KL, Bonakdar M, et al. Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making. Mol Case Stud. 2018;4(2):a002626.CrossRef

Chen DT, Davis-Yadley AH, Huang PY, Husain K, Centeno BA, Permuth-Wey J, Pimiento JM, Malafa M. Prognostic fifteen-gene signature for early stage pancreatic ductal adenocarcinoma. PLoS One. 2015;10(8):e0133562. https://doi.org/10.1371/journal.pone.0133562.CrossRefPubMedPubMedCentral

Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, Szcześniak MW, Gaffney DJ, Elo LL, Zhang X, Mortazavi A. A survey of best practices for RNA-seq data analysis. Genome Biol. 2016;17:13. https://doi.org/10.1186/s13059-016-0881-8.CrossRefPubMedPubMedCentral

Gao C, Zhuang J, Zhou C, Ma K, Zhao M, Liu C, Liu L, Li H, Feng F, Sun C. Prognostic value of aberrantly expressed methylation gene profiles in lung squamous cell carcinoma: a study based on the cancer genome atlas. J Cell Physiol. 2019;234(5):6519–28. https://doi.org/10.1002/jcp.27389.CrossRefPubMed

10.

Garrido P, Conde E, de Castro J, Gómez-Román JJ, Felip E, Pijuan L, Isla D, Sanz J, Paz-Ares L, López-Ríos F. Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a national consensus of the spanish society of pathology and the spanish society of medical oncology. Clin Transl Oncol. 2019;. https://doi.org/10.1007/s12094-019-02218-4.CrossRefPubMedPubMedCentral

11.

Győrffy B, Surowiak P, Budczies J, Lánczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One. 2013;8(12):e82241.CrossRefPubMedPubMedCentral

12.

Jiao Y, Li Y, Jiang P, Han W, Liu Y. Pgm5: a novel diagnostic and prognostic biomarker for liver cancer. PeerJ. 2019;7:e7070. https://doi.org/10.7717/peerj.7070.CrossRefPubMedPubMedCentral

13.

Larrosa R, Arroyo M, Bautista R, López-Rodríguez CM, Claros MG. Neartrans can identify correlated expression changes between retrotransposons and surrounding genes in human cancer. In: Rojas I, Ortuño F, editors. Lecture notes in bioinformatics, IWBBIO18, vol. 10813. Berlin: Srirnger; 2018. p. 373–82.

14.

Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12(1):8. https://doi.org/10.1186/s13073-019-0703-1.CrossRefPubMedPubMedCentral

15.

Mattie M, Raitano A, Morrison K, Morrison K, An Z, Capo L, Verlinsky A, Leavitt M, Ou J, Nadell R, et al. The discovery and preclinical development of asg-5me, an antibody-drug conjugate targeting slc44a4-positive epithelial tumors including pancreatic and prostate cancer. Mol Cancer Ther. 2016;15(11):2679–87. https://doi.org/10.1158/1535-7163.mct-16-0225.CrossRefPubMed

16.

McHugh D, Eisenberger M, Heath EI, Bruce J, Danila DC, Rathkopf DE, Feldman J, Slovin SF, Anand B, Chu R, Lackey J, Reyno L, Antonarakis ES, Morris MJ. A phase i study of the antibody drug conjugate asg-5me, an slc44a4-targeting antibody carrying auristatin e, in metastatic castration-resistant prostate cancer. Investig New Drugs. 2019;37(5):1052–60. https://doi.org/10.1007/s10637-019-00731-5.CrossRef

17.

Nagy Á, Lánczky A, Menyhárt O, Győrffy B. Validation of mirna prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227. https://doi.org/10.1038/s41598-018-27521-y.CrossRefPubMedPubMedCentral

18.

Pan D, Chen J, Feng C, Wu W, Wang Y, Tong J, Zhou D. Preferential localization of muc1 glycoprotein in exosomes secreted by non-small cell lung carcinoma cells. Int J Mol Sci. 2019;. https://doi.org/10.3390/ijms20020323.CrossRefPubMedPubMedCentral

19.

Rodríguez N, Viñal D, Rodríguez-Cobos J, De Castro J, Domínguez G. Genomic profiling in oncology clinical practice. Clin Transl Oncol. 2020;. https://doi.org/10.1007/s12094-020-02296-9 (In press).CrossRefPubMed

20.

Romay LM, González JG, Mateos LL. Cáncer de pulmón y biopsia líquida: realidades y retos en la práctica clínica. Arch Bronconeumol. 2019;55(6):289–90.

21.

Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, Ea Bergbower, Guan Y, Shin J, Guillory J, Rivers CS, Foo CK, Bhatt D, Stinson J, Gnad F, Haverty PM, Gentleman R, Chaudhuri S, Janakiraman V, Jaiswal BS, Parikh C, Yuan W, Zhang Z, Koeppen H, Wu TD, Stern HM, Yauch RL, Huffman KE, Paskulin DD, Illei PB, Varella-Garcia M, Gazdar AF, de Sauvage FJ, Bourgon R, Minna JD, Brock MV, Seshagiri S. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44(10):1111–6. https://doi.org/10.1038/ng.2405.CrossRefPubMedPubMedCentral

22.

Seijo LM, Trujillo JC, Zulueta JJ. Screening in lung cancer: the latest evidence. Arch Bronconeumol. 2019;. https://doi.org/10.1016/j.arbres.2019.04.019.CrossRefPubMed

23.

Shan G, Sheng Z, Xu G, Chen L, Wang X. Analyses of a panel of transcripts identified from a small sample size and construction of rna networks in hepatocellular carcinoma. Front Genet. 2019;10:431.CrossRefPubMedPubMedCentral

24.

Spencer DH, Ley TJ. Sequencing of tumor dna to guide cancer risk assessment and therapy. JAMA. 2018;319(14):1497–8. https://doi.org/10.1001/jama.2018.2281.CrossRefPubMed

25.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. Gepia: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102. https://doi.org/10.1093/nar/gkx247.CrossRefPubMedPubMedCentral

26.

Wang Y, Xia J, Fang Z, Li F, Li D, Wang Z, Feng Y, Zhang J, Chen H, Ji H, Liu H. A novel bmx variant promotes tumor cell growth and migration in lung adenocarcinoma. Oncotarget. 2017;8(20):33405–15. https://doi.org/10.18632/oncotarget.16796.CrossRefPubMedPubMedCentral

27.

Wang Z, Gerstein M, Snyder M. Rna-seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63. https://doi.org/10.1038/nrg2484.CrossRefPubMedPubMedCentral

28.

Xiao J, Lu X, Chen X, Zou Y, Liu A, Li W, He B, He S, Chen Q. Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma. Oncotarget. 2017;8(42):71759.CrossRefPubMedPubMedCentral

29.

Xu T, Li D, Wang H, Zheng T, Wang G, Xin Y. Muc1 downregulation inhibits non-small cell lung cancer progression in human cell lines. Exp Ther Med. 2017;14(5):4443–7.PubMedPubMedCentral

30.

Zhan C, Yan L, Wang L, Sun Y, Wang X, Lin Z, Zhang Y, Shi Y, Jiang W, Wang Q. Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma. J Thorac Dis. 2015;7(8):1398–405. https://doi.org/10.3978/j.issn.2072-1439.2015.07.25.CrossRefPubMedPubMedCentral

Title: Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer
Authors: M. Arroyo
R. Larrosa
J. Gómez-Maldonado
M. Á. Cobo
M. G. Claros
R. Bautista
Publication date: 01-10-2020
Publisher: Springer International Publishing
Keywords: Lung Cancer
Lung Cancer
SCLC
Lung Cancer
SCLC
Biomarkers
Published in: Clinical and Translational Oncology / Issue 10/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-020-02328-4

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