Molecular classification of gastric cancer: A new paradigm Journal Article


Authors: Shah, M. A.; Khanin, R.; Tang, L.; Janjigian, Y. Y.; Klimstra, D. S.; Gerdes, H.; Kelsen, D. P.
Article Title: Molecular classification of gastric cancer: A new paradigm
Abstract: Purpose: Gastric cancer may be subdivided into 3 distinct subtypes-proximal, diffuse, and distal gastric cancer-based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design: Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results: Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions: Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.
Keywords: adult; controlled study; human tissue; aged; major clinical study; histopathology; cancer localization; cancer staging; laparoscopy; preoperative evaluation; gene expression; cancer screening; stomach cancer; down regulation; upregulation; cancer classification; endoscopic biopsy; rna processing; stomach adenocarcinoma; gastroscopy; prostate stem cell antigen; complementary dna; occult cancer
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-05-01
Start Page: 2693
End Page: 2701
Language: English
DOI: 10.1158/1078-0432.ccr-10-2203
PROVIDER: scopus
PMCID: PMC3100216
PUBMED: 21430069
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Hans Gerdes
    125 Gerdes
  2. Yelena Yuriy Janjigian
    145 Janjigian
  3. David S Klimstra
    843 Klimstra
  4. Manish Shah
    173 Shah
  5. Laura Hong Tang
    319 Tang
  6. Raya Khanin
    38 Khanin
  7. David P Kelsen
    332 Kelsen