Gastric cancer recurrence linked to CD44 gene

Polymorphisms of the CD44 gene could help identify patients with gastric cancer who are at increased risk of tumor recurrence, according to investigators who analyzed blood and tissue samples from 137 patients.

Gastric cancer patients with either of two alleles relapsed nearly 5 years earlier than did other patients without these variants, reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

“The CD44 pathway might be a potential target for drug development,” said a fellow at the comprehensive cancer center of the University of Southern California in Los Angeles. CD44 genotyping also can help identify subgroups at high risk for poor clinical outcome.

The researchers obtained blood or formalin-fixed, paraffin-embedded tissue specimens from 137 patients, including 54 women, with localized stages II and III gastric cancer. Over a median follow-up of 3.3 years, 45% of patients had a tumor recurrence with a 3 years probability of recurrence of 0.52.

“Selected polymorphisms because of their potential impact on [messenger RNA] stability and transcription, and a minor allele frequency of more than 10%.

High CD44 protein expression has been associated with poor prognosis in gastric cancer. He noted that another research group, led by Columbia University in New York, recently found that CD44-positive gastric cancer cells show stem cell properties of self-renewal, longevity, and multi-potency.

Also discovered that CD44 overexpression is associated with chemo- (5-flourouracil and etoposide) and radioresistance in a gastric cancer model, and that knockdown of CD44 inhibits the growth of gastric cancer cells in vivo.

“The study by Winder et al, is consistent with the notion that CD44 is more than simply a marker for gastric cancer stem cells but that its expression also promotes gastric cancer growth. Further work is needed to determine whether stratifying patients based on levels of CD44 expression, and/or CD44 for therapy, will improve the outcomes in gastric cancer.”