Serum proteomic patterns for gastric lesions as revealed by SELDI mass spectrometry

https://doi.org/10.1016/j.yexmp.2006.04.008Get rights and content

Abstract

SELDI mass spectrometry was used to investigate protein expression in sera of patients with gastric cancer and gastritis compared to normal volunteers. Differences in peak morphology and intensity were observed in regions of 5910 Da, 5084 Da, 6640 Da and 8691 Da. Patients with gastric cancer exhibited an up-regulation of the 5910 Da peak and a down-regulation of the 8691 Da peak compared to the healthy volunteers; there was also some bi-partitioning and tri-partitioning at the 5084 Da peak. When comparing the sera of these cancer patients with those of gastritis, the former had an up-regulation of the 5910 Da peak and a down-regulation of the 6640 Da peak. This is the first report showing that SELDI sera analysis may be useful in the screening of gastric lesions.

Introduction

Gastric cancer is a debilitating disease associated with a high mortality. Its successful treatment relies on an early diagnosis, but this remains a challenge since the progression of the malignancy is usually silent until it reaches a more advanced stage where the prognosis is poor. Certainly, early detection can drastically facilitate treatment and improve the long-term survival of the patient (Kodera et al., 2003, Leung and Sung, 2002, Makela et al., 2000, Yuan et al., 1999).

The sensitivity of the current single biomarkers in tumor diagnosis is low (usually less than 40%) and complicated by a high return of ‘false-positives’. Further, none of the existing serum markers can be used individually for screening for gastric cancer (Carpelan-Holmstrom et al., 2002, Grotzinger et al., 2001, Ohata et al., 2005, Pan et al., 2003, Roboz, 2005, Schneider et al., 2005). It would be highly desirable to have a new rapid and sensitive diagnostic test for gastric cancer.

Clearly, the use of single biomarkers to diagnose gastric cancer has disadvantages. It is a logical step, therefore, to explore the possibility that a use of a combination of biomarkers could improve diagnostic power. Proteomics is the large-scale study of proteins, or the simultaneous measurement of a large number of expressed proteins (Conrads et al., 2004, Petricoin et al., 2002a, Petricoin et al., 2002b). Proteomic profiling enables a new approach to the discovery of biomarkers in disease (Conrads et al., 2004, Roboz, 2005, Simpkins et al., 2005, Solassol et al., 2005). It has recently been shown to be useful in identifying biomarkers for the diagnosis of bladder, prostate (Roboz, 2005), ovary (Conrads et al., 2004, Petricoin et al., 2002a), breast (Laronga et al., 2003–2004, Li et al., 2005, Roboz, 2005), liver malignancies and other cancers (Roboz, 2005).

Modern proteomic profiling involves ProteinChip technology that sometimes utilizes an enhanced surface laser desorption/ionization (SELDI) time of flight mass spectrometry system (Simpkins et al., 2005). The SELDI assay and detection system has not been used for the profiling of protein clusters in gastric cancer. In the present studies, therefore, we employed SELDI to probe for serum proteins that may be expressed in patients with gastric cancer. We addressed the possibility that serum proteins critical to the progression of gastric cancer can be identified through the changes in peptide/protein mass spectral patterns. We also investigated if such potential changes in spectral patterns are discriminatory of patients with gastritis compared to healthy volunteers.

Section snippets

Patients and volunteers

Studies were conducted using Chinese patients diagnosed with gastric cancer (invasive gastric adenocarcinoma, n = 45), or gastritis (chronic superficial gastritis, n = 40) patients at Tiazhou Municipal Hospital, Zhejian, China. Comparative studies were also performed using healthy volunteers (n = 42). The studies were approved by the local Ethics Committee of Taizhou Municipal Hospital, and had the informed consent of the patients and volunteers.

Sample collection

Approximately 5 ml of blood was withdrawn via

Stage 1: biomarker characteristics of serum from gastric cancer and gastritis patients and normal volunteers

A comparison of protein mass spectra obtained from the sera of the gastric cancer group and the healthy volunteer group revealed 45 protein peaks. There were statistical differences between 3 protein peaks located at 5910 Da, 5084 Da and 8691 Da (P < 0.05); the intensity of protein peaks at 5910 Da in the sera from patients with gastric cancer was clearly higher than that of the healthy controls (P < 0.05). Bi-peak or tri-peaks at 5084 Da were also observed in the sera from patients with

Discussion

Early diagnosis improves the long-term survival chances of patients with stomach cancers (see Introduction). However, one of the features of nearly all human cancers is that there is molecular heterogenicity, meaning that screening for a single diagnostic marker is not efficient, with some patients not being correctly diagnosed. A logical development to improve the early diagnosis of cancer is to therefore simultaneously screen for multiple biomarkers to increase the probability of detection (

References (24)

  • R.L. Hamler et al.

    A two-dimensional liquid-phase separation method coupled with mass spectrometry for proteomic studies of breast cancer and biomarker identification

    Proteomics

    (2004)
  • Y. Kodera et al.

    Follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit

    Ann. Surg. Oncol.

    (2003)
  • Cited by (0)

    View full text