TY - JOUR
T1 - Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery
AU - Pawar, Harsh
AU - Kashyap, Manoj Kumar
AU - Sahasrabuddhe, Nandini A.
AU - Renuse, Santosh
AU - Harsha, H. C.
AU - Kumar, Praveen
AU - Sharma, Jyoti
AU - Kandasamy, Kumaran
AU - Marimuthu, Arivusudar
AU - Nair, Bipin
AU - Rajagopalan, Sudha
AU - Maharudraiah, Jagadeesha
AU - Premalatha, Chennagiri Shrinivasamurthy
AU - Kumar, Kariyanakatte Veeraiah Veerendra
AU - Vijayakumar, M.
AU - Chaerkady, Raghothama
AU - Prasad, Thotterthodi Subrahmanya Keshava
AU - Kumar, Rekha V.
AU - Pandey, Akhilesh
N1 - Funding Information:
We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics. T.S.K.P. and R.V.K. are supported by DBT grant (DBT/CSH/ GIA/1583/2010–2011). T.S.K.P. is also a recipient of young investigator award from DBT, India. H.G. is a Wellcome Trust/DBT India Alliance Early Career Fellow. H.P., N.A.S. and J.S. are recipients of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. S.R. is a recipient of Senior Research Fellowship from University Grants Commission (UGC), Government of India. We would also like to thank Drs. S. Krishna Murthy and Vijayalaxmi Deshmane of Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, for providing tissue samples for this study. We would like to thank Drs. S.K. Shankar and Anita Mahadevan of National Institute of Mental Health and Neurological Sciences (NIMHANS), for providing access to the imaging facility. We thank Agilent Technologies for access to instrumentation.
PY - 2011/9/15
Y1 - 2011/9/15
N2 - 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 performed 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 with 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.
AB - 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 performed 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 with 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.
KW - Early detection
KW - Esophageal carcinoma
KW - Invasion
KW - Mass spectrometry
KW - Metastasis
KW - Progression
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U2 - 10.4161/cbt.12.6.16833
DO - 10.4161/cbt.12.6.16833
M3 - Article
C2 - 21743296
AN - SCOPUS:80052855504
SN - 1538-4047
VL - 12
SP - 510
EP - 522
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 6
ER -