Abstract
4110 Background: The clinical significance of cancer stem cells (CSC) has been well established; however, its prognostic role remains controversial. CD44 is recognized as a CSC marker in gastric cancer (GC) and, recently, the clinical impact of CD166 in GC was reported. Our group previously reported SNPs of CD44 and CD166 are associated with outcome in US patients (pts) with adjuvant GC and colorectal cancer, respectively. Since GC has regional differences in epidemiology and clinicopathology, we hypothesized that ethnicity and regional differences in GC could influence the prognostic role of CD44 and CD166. Methods: A total of 369 pts with histopathologically-confirmed localized (stage Ib to IV; AJCC-6th) GC were enrolled from Japan (n=169), the US (n=137), and Austria (n=63) between 2002 and 2010. CD44 rs187116 G>A and CD166 rs1157 G>A were analyzed. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Results: Pts homozygous for A/A CD44rs187116 (n=20) showed a median OS of 2.0 yrs vs not reached for patients harboring at least one-G allele (n=144) (HR: 2.87 [95%CI: 1.61-5.13], p<0.001) in Japanese cohort, while pts homozygous A/A (n=30) showed a median OS of 7.3 yrs vs 4.1 yrs for pts harboring at least one-G allele (n=94) (HR: 2.0 [95%CI: 0.90-4.55], p=0.079) in the US cohort. There were no significant differences in Austrian cohort alone or in combination with US cohort. In CD166 rs1157, pts harboring at least one-A allele (n=27) showed a median OS of 3.9 yrs vs not reached for pts homozygous G/G (n=142) (HR: 1.81 [95%CI: 1.05-3.12], p=0.033) in Japanese cohort., Although there were no significant differences in the US or Austrian cohort when analyzed separately, combining cohorts demonstrated that pts homozygous A/A (n=12) showed a median OS of not reached yrs vs 4.7 yrs for pts harboring at least one-G allele (n=179) (HR: 5.00 [95%CI: 0.70-35.95], p=0.073). Conclusions: SNP profiles in CSC markers predicted opposite prognostic outcomes in patients with GC among Asian and Western countries. This is the first report suggesting that the prognostic role of CSC markers in GC may differ based on ethnic groups or etiology differences.
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