Research article

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

Oi Lian Kon¹ , Tai-Tung Yip² , Meng Fatt Ho¹ , Weng Hoong Chan³ , Wai Keong Wong³ , Soo Yong Tan⁴ , Wai Har Ng¹ , Siok Yuen Kam¹ , Alvin KH Eng^1,2 , Patrick Ho² , Rosa Viner² , Hock Soo Ong³ and M Priyanthi Kumarasinghe⁴

¹Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Republic of Singapore

²Ciphergen Biosystems Inc., Fremont, USA

³Department of General Surgery, Singapore General Hospital, Singapore, Republic of Singapore

⁴Department of Pathology, Singapore General Hospital, Singapore, Republic of Singapore

author email corresponding author email

BMC Medical Genomics 2008, 1:54doi:10.1186/1755-8794-1-54

Published:	25 October 2008

Abstract

Background

Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.

Methods

Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.

Results

By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.

Conclusion

This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.