Identification of differentially expressed serum proteins in gastric adenocarcinoma

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.

Sex hormone‐binding globulin (SHBG) is a potential early diagnostic biomarker for gastric cancer

“…This finding supports a recently published study which reported a 2.3‐fold increase in plasma SHBG level in GC patients compared to a control group as measured by iTRAQ‐based quantitative MS. However, that study did not validate plasma SHBG level in different study cohorts .…”

Peripheral versus Central Index of Metabolic Dysfunction and Associations with Clinical and Pathological Outcomes in Alzheimer’s Disease

“…For example, transgenic mice that overexpressed IGFBP-2 showed significantly higher blood glucose levels than controls at 30, 60 and 90 minutes during an oral glucose tolerance test, as well as lower levels of GLUT4–the insulin-dependent glucose transporter–at cell surfaces compared to controls [5]. Abnormally high IGFBP-2 levels are often an indicator of severe catabolic events, such as gastric cancer, anorexia nervosa and renal failure [6-8]. In a study of 625 men and women aged 70 and older, plasma IGFBP-2 significantly predicted mortality from all causes after adjusting for markers of body composition, as well as fasting glucose and insulin [9].…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…The Polysulfoethyl columns from Poly‐LC (Neste group) have been by far the most widely used column type. Notable examples where SCX fractionation has been used include the study by Juhasz et al where it was used in combination with tandem depletion and LC‐MALDI, reporting 470 proteins detected in nine iTRAQ experiments, the ESI study of gastric adenocarcinoma by Subbannayya et al where they reported identification 643 proteins, and the ESI & MALDI study of Zhang et al where they reported 1044 proteins . SCX fractionation has mostly been performed off‐line, necessitating additional concentration and desalting steps.…”