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


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.

SUBMITTER: Kon OL 

PROVIDER: S-EPMC2584050 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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

Kon Oi Lian OL   Yip Tai-Tung TT   Ho Meng Fatt MF   Chan Weng Hoong WH   Wong Wai Keong WK   Tan Soo Yong SY   Ng Wai Har WH   Kam Siok Yuen SY   Eng Alvin Kh AKh   Ho Patrick P   Viner Rosa R   Ong Hock Soo HS   Kumarasinghe M Priyanthi MP  

BMC medical genomics 20081025


<h4>Background</h4>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.<h4>Methods</h4>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enha  ...[more]

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