title: Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery.
abstract: Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange chromatography fractions was carried out on an Accurate Mass QTOF mass spectrometer, which led to the identification of 687 proteins. In all, 257 proteins were identified as differentially expressed in ESCC as compared to normal. We found several previously known protein biomarkers to be upregulated in ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70 kDa protein 9 (HSPA9) confirming the validity of our approach. In addition, several novel proteins that had not been reported previously were identified in our screen. These novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays. The success of our study shows that this mass spectrometric strategy can be applied to cancers in general to develop a panel of candidate biomarkers, which can then be validated by other techniques.
authors: Institute of Bioinformatics, International Technology Park, Bangalore, India.
authors: Harsh
authors: H
authors: Pawar
authors: Manoj Kumar
authors: MK
authors: Kashyap
authors: Nandini A
authors: NA
authors: Sahasrabuddhe
authors: Santosh
authors: S
authors: Renuse
authors: H C
authors: HC
authors: Harsha
authors: Praveen
authors: P
authors: Kumar
authors: Jyoti
authors: J
authors: Sharma
authors: Kumaran
authors: K
authors: Kandasamy
authors: Arivusudar
authors: A
authors: Marimuthu
authors: Bipin
authors: B
authors: Nair
authors: Sudha
authors: S
authors: Rajagopalan
authors: Jagadeesha
authors: J
authors: Maharudraiah
authors: Chennagiri Shrinivasamurthy
authors: CS
authors: Premalatha
authors: Kariyanakatte Veeraiah Veerendra
authors: KV
authors: Kumar
authors: M
authors: M
authors: Vijayakumar
authors: Raghothama
authors: R
authors: Chaerkady
authors: Thotterthodi Subrahmanya Keshava
authors: TS
authors: Prasad
authors: Rekha V
authors: RV
authors: Kumar
authors: Rekha V
authors: RV
authors: Kumar
authors: Akhilesh
authors: A
authors: Pandey
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D055088:Early Detection of Cancer; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051190:Plectin / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D049231:Saposins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; C495332:PLEC protein, human; C483345:PSAP protein, human; D051190:Plectin; D020543:Proteome; D049231:Saposins; C526505:PDIA4 protein, human; D019704:Protein Disulfide-Isomerases