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Cancer Cell International
Published in: Cancer Cell International 1/2010

Open Access 01-12-2010 | Primary research

Identification and validation of genes involved in gastric tumorigenesis

Authors: Thangarajan Rajkumar, Neelakantan Vijayalakshmi, Gopisetty Gopal, Kesavan Sabitha, Sundersingh Shirley, Uthandaraman M Raja, Seshadri A Ramakrishnan

Published in: Cancer Cell International | Issue 1/2010

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Abstract

Background

Gastric cancer is one of the common cancers seen in south India. Unfortunately more than 90% are advanced by the time they report to a tertiary centre in the country. There is an urgent need to characterize these cancers and try to identify potential biomarkers and novel therapeutic targets.

Materials and methods

We used 24 gastric cancers, 20 Paired normal (PN) and 5 apparently normal gastric tissues obtained from patients with non-gastric cancers (Apparently normal - AN) for the microarray study followed by validation of the significant genes (n = 63) by relative quantitation using Taqman Low Density Array Real Time PCR. We then used a custom made Quantibody protein array to validate the expression of 15 proteins in gastric tissues (4 AN, 9 PN and 9 gastric cancers). The same array format was used to study the plasma levels of these proteins in 58 patients with gastric cancers and 18 from patients with normal/non-malignant gastric conditions.

Results

Seventeen genes (ASPN, CCL15/MIP-1δ, MMP3, SPON2, PRSS2, CCL3, TMEPAI/PMEPAI, SIX3, MFNG, SOSTDC1, SGNE1, SST, IGHA1, AKR1B10, FCGBP, ATP4B, NCAPH2) were shown to be differentially expressed between the tumours and the paired normal, for the first time. EpCAM (p = 0.0001), IL8 (p = 0.0003), CCL4/MIP-1β (p = 0.0026), CCL20/MIP-3α (p = 0.039) and TIMP1 (p = 0.0017) tissue protein levels were significantly different (Mann Whitney U test) between tumours versus AN & PN. In addition, median plasma levels of IL8, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, PDGFR-B and TIMP1 proteins were significantly different between the non-malignant group and the gastric cancer group. The post-surgical levels of EpCAM, IGFBP3, IL8, CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, SPP1/OPN and PDGFR-B showed a uniform drop in all the samples studied.

Conclusions

Our study has identified several genes differentially expressed in gastric cancers, some for the first time. Some of these have been confirmed at the protein level, as well. Some of these proteins will need to be evaluated further for their potential as diagnostic biomarkers in gastric cancers and some could be useful as follow-up markers in gastric cancer.
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Metadata
Title
Identification and validation of genes involved in gastric tumorigenesis
Authors
Thangarajan Rajkumar
Neelakantan Vijayalakshmi
Gopisetty Gopal
Kesavan Sabitha
Sundersingh Shirley
Uthandaraman M Raja
Seshadri A Ramakrishnan
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2010
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-10-45

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