PDF
Abstract
Aim: To identify serum biomarkers for non-small cell lung cancer (NSCLC) and assess their potential for early diagnosis.
Experimental: MB-WCX coupled with MALDI-TOF MS was utilized to profile serum samples from 64 NSCLC patients and 64 healthy subjects, followed by ClinProTools software and Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) for recognition and characterization of differentially expressed peaks. Enzyme-linked immunosorbent assay (ELISA) confirmed protein concentrations, while The Cancer Genome Atlas (TCGA) database was leveraged for validation of candidate biomarkers in a larger cohort.
Results: 39 distinct proteomic m/z peaks were identified for NSCLC subjects, with five of these peaks significantly distinguishing NSCLC from healthy controls (HC). A model developed using the GA (Genetic Algorithm) with ClinProt data demonstrated a sensitivity of 84.72% and a specificity of 88.68% in identifying NSCLC patients. Peaks 2 through 5 were observed to be downregulated in the NSCLC group. Notably, a peptide peak, Peak 1, with an m/z value of 1,866, identified as a fragment of TUBB, was upregulated in NSCLC. ELISA validated the increased serum TUBB levels in NSCLC patients (P < 0.001). Furthermore, analysis of TUBB expression in lung cancer tissues through TCGA data revealed elevated TUBB expression in lung cancer tissues.
Conclusions: Serum TUBB is identified as a potential diagnostic biomarker for NSCLC, which may benefit early diagnosis and enhance the survival rate of NSCLC patients.
Keywords
NSCLC
/
proteomic
/
serum biomarker
/
TUBB
Cite this article
Download citation ▾
Ning Du, Dingli Song, Dapeng Liu, Xin Liu, Xin Sun, Guangjian Zhang, Hong Ren, Yunfeng Zhang.
Serum TUBB is a potential biomarker for the diagnosis of non-small cell lung cancer.
Journal of Cancer Metastasis and Treatment, 2025, 11: 9 DOI:10.20517/2394-4722.2024.127
| [1] |
Sung H,Siegel RL.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2021;71:209-49
|
| [2] |
Imyanitov EN,Levchenko EV.Molecular testing and targeted therapy for non-small cell lung cancer: current status and perspectives.Crit Rev Oncol Hematol2021;157:103194
|
| [3] |
Duffy MJ.Chapter One - Tissue and blood biomarkers in lung cancer: a review.Adv Clin Chem2018;86:1-21
|
| [4] |
Shi JF,Wu N.Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: overall design and results from a multicenter retrospective epidemiologic survey.Lung Cancer2019;128:91-100
|
| [5] |
Osmani L,Gabrielson E.Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): moving from targeted therapy to immunotherapy.Semin Cancer Biol2018;52:103-9 PMCID:PMC5970946
|
| [6] |
Hoseok I.Chapter Three - Lung cancer biomarkers.Adv Clin Chem2015;72:107-70
|
| [7] |
Thakur MK.Predictive and prognostic biomarkers in non-small cell lung cancer.Semin Respir Crit Care Med2016;37:760-70
|
| [8] |
Duan B,Qiu J.Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients.EBioMedicine2018;37:134-43 PMCID:PMC6284455
|
| [9] |
He A,Huang C.Detection of serum tumor markers in multiple myeloma using the CLINPROT system.Int J Hematol2012;95:668-74
|
| [10] |
Risha Y,Ghobadloo SM.The proteomic analysis of breast cell line exosomes reveals disease patterns and potential biomarkers.Sci Rep2020;10:13572 PMCID:PMC7419295
|
| [11] |
Tsuchida S,Takiwaki M.Current status of proteomic technologies for discovering and identifying gingival crevicular fluid biomarkers for periodontal disease.Int J Mol Sci2018;20:86 PMCID:PMC6337088
|
| [12] |
Murphy S,Mundegar RR,Ohlendieck K.Proteomic serum biomarkers for neuromuscular diseases.Expert Rev Proteomic2018;15:277-91
|
| [13] |
Geyer PE,Teupser D.Revisiting biomarker discovery by plasma proteomics.Mol Syst Biol2017;13:942 PMCID:PMC5615924
|
| [14] |
Kisluk J,Niemira M,Niklinski J.Proteomics biomarkers for non-small cell lung cancer.J Pharm Biomed Anal2014;101:40-9
|
| [15] |
Zhu Z,Huo S,Cao X.TUBB, a robust biomarker with satisfying abilities in diagnosis, prognosis, and immune regulation via a comprehensive pan-cancer analysis.Front Mol Biosci2024;11:1365655 PMCID:PMC11096532
|
| [16] |
Mariani M,Spennato M.Class III β-tubulin in normal and cancer tissues.Gene2015;563:109-14 PMCID:PMC6649683
|
| [17] |
Yu X,Wu B,Pertsemlidis A.The miR-195 axis regulates chemoresistance through TUBB and lung cancer progression through BIRC5.Mol Ther Oncolytics2019;14:288-98 PMCID:PMC6727248
|
| [18] |
Yeh IT.The betaII isotype of tubulin is present in the cell nuclei of a variety of cancers.Cell Motil Cytoskeleton2004;57:96-106
|
| [19] |
Dumontet C.Microtubule-binding agents: a dynamic field of cancer therapeutics.Nat Rev Drug Discov2010;9:790-803 PMCID:PMC3194401
|
| [20] |
Kavallaris M.Microtubules and resistance to tubulin-binding agents.Nat Rev Cancer2010;10:194-204
|
| [21] |
Bouras G,Fujita Y,Takubo T.Identification of β-tubulin as a common immunogen in gastrointestinal malignancy by mass spectrometry of colorectal cancer proteome: implications for early disease detection.Anal Bioanal Chem2012;403:1801-9
|
| [22] |
He Q,Zhuang D.Clinicopathological significance of β-tubulin isotype III gene expression in breast cancer patients.Cancer Biomark2015;15:823-31
|
| [23] |
Zhao X,Chen J.Class III β-tubulin in colorectal cancer: tissue distribution and clinical analysis of chinese patients.Med Sci Monit2016;22:3915-24 PMCID:PMC5088737
|
| [24] |
De Donato M,Petrella L.Class III β-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer.J Cell Physiol2012;227:1034-41
|
| [25] |
Fan NJ,Ge XY.Identification alpha-2-HS-glycoprotein precursor and tubulin beta chain as serology diagnosis biomarker of colorectal cancer.Diagn Pathol2014;9:53 PMCID:PMC3975189
|
| [26] |
Sève P,Dumontet C.The role of betaIII tubulin in predicting chemoresistance in non-small cell lung cancer.Lung Cancer2010;67:136-43
|
| [27] |
Maahs L,Gupta N.Class III β-tubulin expression as a predictor of docetaxel-resistance in metastatic castration-resistant prostate cancer.PLoS One2019;14:e0222510 PMCID:PMC6816559
|
| [28] |
Ruksha K,Nerovnya A.Over-expression of βII-tubulin and especially its localization in cell nuclei correlates with poorer outcomes in colorectal cancer.Cells2019;8:25 PMCID:PMC6357106
|
| [29] |
Gao J,Peng K.[Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types].Nan Fang Yi Ke Da Xue Xue Bao2022;42:886-91
|
| [30] |
Goldstraw P,Crowley J.The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer.J Thorac Oncol2016;11:39-51
|