Gastric Cancer-Specific Protein Profile Identified Using Endoscopic Biopsy Samples via MALDI Mass Spectrometry

Abstract

To date, proteomic analyses on gastrointestinal cancer tissue samples have been performed using surgical specimens only, which are obtained after a diagnosis is made. To determine if a proteomic signature obtained from endoscopic biopsy samples could be found to assist with diagnosis, frozen endoscopic biopsy samples collected from 63 gastric cancer patients and 43 healthy volunteers were analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A statistical classification model was developed to distinguish tumor from normal tissues using half the samples and validated with the other half. A protein profile was discovered consisting of 73 signals that could classify 32 cancer and 22 normal samples in the validation set with high predictive values (positive and negative predictive values for cancer, 96.8% and 91.3%; sensitivity, 93.8%; specificity, 95.5%). Signals overexpressed in tumors were identified as α-defensin-1, α-defensin-2, calgranulin A, and calgranulin B. A protein profile was also found to distinguish pathologic stage Ia (pT1N0M0) samples (n = 10) from more advanced stage (Ib or higher) tumors (n = 48). Thus, protein profiles obtained from endoscopic biopsy samples may be useful in assisting with the diagnosis of gastric cancer and, possibly, in identifying early stage disease.

Imaging of Intact Tissue Sections: Moving beyond the Microscope

“…Imaging and profiling of proteins have been applied to a wide variety of tissues and diseases, including brain (8,9), breast (10 -12), gastric (13), lung (14), kidney (5), and prostate (15) cancer; embryonic development (16); inflammatory bowel diseases (17); and Alzheimer disease (18). Several of these studies are described in some detail below.…”

“…A recent study employing IMS technology examined 106 gastric biopsy samples from 63 cancer patients and 43 healthy volunteers to determine a molecular signature of gastric cancer (13). A histology-directed protein profiling approach was used to target areas enriched (Ͼ75%) in either carcinoma or normal epithelial cells.…”

MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications

“…Such techniques that have already been employed in the field of MALDI-IMS are the significance analysis of microarrays (Bauer et al 2010;Hardesty et al 2011;Tusher et al 2001), the permutation t test , the weighted flexible compound covariate method (Schwartz et al 2005) and the receiver operating characteristics analysis (Balluff et al 2010). If classical MannWhitney U test/Kruskal-Wallis test or t test/ANOVA is applied, the resulting significance values should be corrected by multiple testing methods such as BenjaminiHochberg to control for the false discovery rate of features (Clarke et al 2008;Kim et al 2010).…”

“…Comparing lymph nodes of classical Hodgkin lymphoma with lymph nodes of inflammatory changes resulted in a classification model that could distinguish the lymph nodes with an overall accuracy of 86.65%. In a study by Kim et al (2010) histology-directed MALDI profiling of 63 gastric cancer and 43 healthy endoscopic biopsies found a protein profile, which classified samples in the validation set with high predictive values as either cancerous or healthy. Furthermore, the protein profile could distinguish pathologic AJCC (American Joint Committee on Cancer) stage Ia from more advanced stage patients (Ib or higher).…”

Imaging mass spectrometry in biomarker discovery and validation

“…Another study on gastric cancer was able to obtain a cancer specific protein profile to distinguish endoscopic biopsy samples with cancer from samples without cancer [72]. In total, fresh frozen endoscopic biopsy samples from 63 gastric cancer patients and 43 healthy volunteers were analyzed using a histology directed approach.…”