Identification of differentially expressed serum proteins in gastric adenocarcinoma

Yashwanth Subbannayya; Sartaj Ahmad Mir; Santosh Renuse; Srikanth S Manda; Sneha M Pinto; Vinuth N Puttamallesh; Hitendra Singh Solanki; H C Manju; Nazia Syed; Rakesh Sharma; Rita Christopher; M Vijayakumar; K V Veerendra Kumar; T S Keshava Prasad; Girija Ramaswamy; Rekha V Kumar; Aditi Chatterjee; Akhilesh Pandey; Harsha Gowda

doi:10.1016/j.jprot.2015.04.021

Identification of differentially expressed serum proteins in gastric adenocarcinoma

J Proteomics. 2015 Sep 8;127(Pt A):80-8. doi: 10.1016/j.jprot.2015.04.021. Epub 2015 May 5.

Authors

Yashwanth Subbannayya¹, Sartaj Ahmad Mir², Santosh Renuse³, Srikanth S Manda⁴, Sneha M Pinto², Vinuth N Puttamallesh⁵, Hitendra Singh Solanki⁵, H C Manju⁵, Nazia Syed⁶, Rakesh Sharma⁷, Rita Christopher⁷, M Vijayakumar⁸, K V Veerendra Kumar⁸, T S Keshava Prasad⁵, Girija Ramaswamy⁹, Rekha V Kumar¹⁰, Aditi Chatterjee⁵, Akhilesh Pandey¹¹, Harsha Gowda¹²

Affiliations

¹ Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Rajiv Gandhi University of Health Sciences, Bangalore 560041, Karnataka, India; Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India.
² Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Manipal University, Manipal 576 104, Karnataka, India.
³ Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India.
⁴ Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India.
⁵ Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
⁶ Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India.
⁷ Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560029, Karnataka, India.
⁸ Department of Surgery, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India.
⁹ Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India.
¹⁰ Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India.
¹¹ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹² Institute of Bioinformatics, International Technology Park, Bangalore 560066, India. Electronic address: [email protected].

Abstract

Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu-Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients.

Biological significance: Gastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well classified patient samples would prove useful in identifying novel blood based biomarkers for gastric cancers. This article is part of a Special Issue entitled: Proteomics in India.

Keywords: Body fluid; In vitro labeling; LC-MS/MS analysis; Mass spectrometry; Serum proteome.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / blood*
Biomarkers, Tumor / blood*
Female
Gene Expression Regulation, Neoplastic*
Humans
Male
Neoplasm Proteins / blood*
Stomach Neoplasms / blood*

Substances

Biomarkers, Tumor
Neoplasm Proteins

Grants and funding

P30 CA006973/CA/NCI NIH HHS/United States