title: Glycosylated Alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker.
abstract: Presently existing screening approaches for lung cancer are not being proving sufficient and sensitive, so a study was conducted to identify disease related biomarker proteins for diagnostic applications. A total of 100 lung cancer patients (88 non-small cell lung cancer and 12 small cell lung cancer) and 50 healthy controls were included in this study. Serum samples of patients and healthy controls were subjected to a series of proteomic approaches and as a result of two dimensional gel electrophoresis, a ∼ 43 kDa protein was found to be differentially expressed compared to healthy controls. Quantitative profiling of two dimensional gels by Dymension software analysis displayed 3.58 fold increased expression of ∼ 43 kDa protein in squamous cell carcinoma and 2.92 fold in case of adenocarcinoma. Mass spectrometric analysis resulted in identification of 8 differentially expressed proteins, out of which human Alpha-1-acid glycoprotein 1 was targeted for further validations. This candidate protein exhibited N-linked glycosylation at five amino acid residues; 33, 56, 72, 93, and 103 with significant score of 0.66, 0.78, 0.78, 0.53 and 0.66, respectively. Sandwich ELISA quantified high serum levels of Alpha-1-acid glycoprotein 1 in squamous cell carcinoma (2.93 g/l ± 1.22) and adenocarcinoma (2.39 g/l ± 1.13) when compared with healthy controls (0.83 g/l ± 0.21). One-way ANOVA analysis predicted highly significant variation of Alpha-1-acid glycoprotein 1, among all the study types (F-value 65.37, p-value 0.000). This study may prove as a non-invasive, cost effective and sensitive scheme for diagnosis of lung cancer, by passing the expensive and painful screening procedures.
authors.affiliation: Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Asima
authors.initials: A
authors.lastname: Ayyub
authors.affiliation: Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore 54590, Pakistan. Electronic address: mahjabeensaleem1@hotmail.com.
authors.forename: Mahjabeen
authors.initials: M
authors.lastname: Saleem
authors.affiliation: School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Iram
authors.initials: I
authors.lastname: Fatima
authors.affiliation: School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan.
authors.forename: Asma
authors.initials: A
authors.lastname: Tariq
authors.affiliation: Hussain Ebrahim Jamal Research Institute, University of Karachi, 75270 Karachi, Pakistan.
authors.forename: Naghma
authors.initials: N
authors.lastname: Hashmi
authors.affiliation: Hussain Ebrahim Jamal Research Institute, University of Karachi, 75270 Karachi, Pakistan.
authors.forename: Syed Ghulam
authors.initials: SG
authors.lastname: Musharraf
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D009961:Orosomucoid / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D009961:Orosomucoid
keywords: 2DE; Cancer; Candidate biomarker; MALDI-TOF/TOF