title: Identification and validation of genes involved in gastric tumorigenesis.
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.
  
  
  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.
authors.affiliation: Dept. of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Thangarajan
authors.initials: T
authors.lastname: Rajkumar
authors.affiliation: Dept. of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Neelakantan
authors.initials: N
authors.lastname: Vijayalakshmi
authors.affiliation: Dept. of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Gopisetty
authors.initials: G
authors.lastname: Gopal
authors.affiliation: Dept. of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Sabitha
authors.affiliation: Dept. of Pathology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Sundersingh
authors.initials: S
authors.lastname: Shirley
authors.affiliation: Dept. of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Uthandaraman M
authors.initials: UM
authors.lastname: Raja
authors.affiliation: Dept. of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600036, India.
authors.forename: Seshadri A
authors.initials: SA
authors.lastname: Ramakrishnan