α1-Antitrypsin Precursor in Gastric Juice Is a Novel Biomarker for Gastric Cancer and Ulcer

Abstract

Purpose: To search for novel disease-specific markers in gastric juice by investigating the protein concentrations and components in gastric juice from patients with various gastroduodenal diseases. Experimental Design: Protein concentrations and pH values in fasting gastric juice were examined in 120 healthy subjects and 39 gastric ulcer, 38 duodenal ulcer, and 31 gastric cancer patients. The protein components in gastric juice were studied by two-dimensional PAGE and mass spectrometric analysis. Results: Protein concentrations in gastric juice of patients with gastric ulcers and gastric cancer were significantly higher than those in healthy subjects (1.06 and 2.61 mg/mL versus 0.48 mg/mL; P = 0.001and P < 0.001, respectively), and duodenal ulcer patients had lower gastric juice protein concentrations compared with healthy subjects (0.26 versus 0.48 mg/mL; P < 0.05). Gastric hypoacidity and advanced age were independent factors affecting the protein concentrations in gastric juice with odds ratios of 32.9 (95% confidence interval, 11.8-90.9) and 3.2 (95% confidence interval, 1.3-8.3), respectively. Each electrophoresis images of gastric juice could be classified into one of three patterns: basic band, specific band, or nonspecific band. The frequencies of specific band pattern in healthy subjects, gastric ulcer, duodenal ulcer, and gastric cancer patients were 6%, 42%, 6%, and 93%, respectively. Proteomic analysis revealed that a1-antitrypsin precursor was the principal peptide in the specific band. Conclusions: a1-antitrypsin precursor in gastric juice is a novel biomarker for gastric cancer and ulcer. A noninvasive method to obtain gastric juice followed by proteomic analysis may serve as a new tool to screen for gastric malignancies.

Diagnosis of Gastric Malignancy Using Gastric Juice α1-antitrypsin

“…Gastric cancer patients had higher frequencies of α1-antitrypsin and albumin peaks and lower frequencies of leucine zipper protein and pepsinogen peaks than healthy subjects (12). Another our study (11) showed a prominent band of α1-antitrypsin in the two-dimensional gastric juice electrophoresis image of gastric juice samples from gastric cancer patients. However, the α1-antitrypsin band seemed not to be cancer specific because a small α1-antitrypsin band was also identified in the gastric juices from 42%, 6%, and 6% of gastric ulcer patients, duodenal ulcer patients, and healthy subjects, respectively.…”

“…In clinical practice, it might be difficult to differentiate gastric cancer from gastric ulcer in some patients with mild elevation of gastric juice α1-antitrypsin concentrations. Our previous study has shown that leukocyte elastase inhibitor, desmoglein-1 precursor, and immunoglobulin κ chain C region were other potential biomarkers for gastric cancer in gastric juices (11). A scoring system using the combination of different measurements, such as the gastric juice pH, protein concentration, α1-antitrypsin, and other biomarker levels, could potentially give more accurate results than a single gastric juice biomarker for the discrimination of gastric cancer and merits further investigations.…”

“…Our recent study established that α1-antitrypsin is a potential biomarker for gastric cancer in gastric juice (11). In addition, several other peptides, such as pepsinogen, leucin zipper protein, and albumin fragments, are also novel candidates in gastric juice for cancer screening (12).…”

Translational Research and Plasma Proteomic in Cancer

“…Proteomic analysis with 2-DE can simultaneously detect changes of multiple proteins in plasma often detected differentially expressed proteins are common abundant plasma proteins and their diagnostic value may be limited. Twodimensional electrophoresis (2-DE) has been used for the discovery of circulating auto-antibodies in cancer patients and annexins I and II were reported as specific antigens in sera from patients with lung [Nolen and Lokshin, 2013]; b-2 microglobulin [Yang et al, 2009] apolipoprotein [Podzielinski et al, 2013]; gene-expression in HE4 [Ferraro et al, 2013 [Du et al, 2013]; AGR2 [Li et al, 2015c]; ubiquitin ligase [Goka and Lippman, 2015]; ferritin light chain [Jezequel et al, 2012] Gastric cancer a1-antitrypsin precursor [Hsu et al, 2007]; pepsinogen C [Terasawa et al, 2014]; Cathepsin B [Ebert et al, 2005]; galectin-1/-3 [Thijssen et al, 2015]; miR-214 [Zhang et al, 2015b]; angiopoietinlike protein 2 [Yoshinaga et al, 2015]; MOR1 [Yao et al, 2015]; circular RNA [Li et al, 2015a] Liver cancer Galectin-1/-3 [Thijssen et al, 2015]; CHI3L1/MASP2 [Ding et al, 2014]; Sall4, Glypican-3, dickkopf-1 and talin-1 [Chatterjee and Mitra, 2015] …”

Acute Phase Proteins as Cancer Biomarkers

“…Several reports have corroborated elevated levels of AAT in gastric juice in patients with gastric cancer compared with healthy controls. (Hsu et al 2007;Lee et al 2004) …”