Abstract
BackgroundGastric 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 methodsWe 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.ResultsSeventeen 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.ConclusionsOur 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.
Highlights
Gastric cancer is one of the common cancers seen in South India, ranked 2nd among men and 5th among women in the Chennai Metropolitan area [1]
Median plasma levels of IL8, CXCL9/MIG, CCL3/MIP-1a, CCL20/MIP-3a, 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-1a, CCL20/MIP-3a, SPP1/OPN and PDGFR-B showed a uniform drop in all the samples studied
Summary
Gastric cancer is one of the common cancers seen in South India, ranked 2nd among men and 5th among women in the Chennai Metropolitan area [1]. Of the patients presenting to the tertiary Institution, more than 90% are advanced at presentation and only palliative management is feasible in these patients [2]. In 2005 and 2006, a total of 1239 gastric cancer patients were seen at the Institute, of which 211 patients had been previously treated elsewhere. In Japan, which has a high incidence of gastric cancer, photofluorography screening is done as a screening program for the population, resulting in early detection of lesions, some confined to mucosa only [3]. Such a procedure is unlikely to be the solution in a large country such as India. There is an urgent need to characterize these cancers and try to identify potential biomarkers and novel therapeutic targets
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
