Gene signature linked to survival after pancreatic-cancer surgery

By David Douglas

NEW YORK (Reuters Health) - 23/4/2019

"This non-invasive biomarker signature can be easily determined at the time of PDAC diagnosis in order to guide personalized treatment decisions and to direct patient stratification in clinical trials," said Dr. Lukasz Filip Grochola of the Cantonal Hospital of Winterthur, Switzerland.

"In addition, due to their inferred functional mechanisms, the identified genetic variants have the potential to guide the development of individualized genomic strategies for PDAC therapies," he told Reuters Health by email.

The results, online April 3 in JAMA Surgery, are based on genome-wide screening of two cohorts of patients who had undergone resection for PDAC.

For identification of high-frequency polymorphic variants associated with allelic differences in tumor-associated survival, the researchers relied on a European cohort of 195 patients. For validation, they used a U.S. cohort of 136 patients.

The team identified two such SNPs in regulatory regions of the CHI3L2 and the CD44 genes. The risk-indicating genotypes were the rs353630 T/T and/or rs684559 A/A genotypes, while the protective genotypes included the rs353630 C allele and rs684559 G allele.

After merging both datasets, the team found that compared with patients who had protective genotypes, those who carried the risk alleles at one of both SNP loci had a 2.63-fold increased risk for tumor-associated death, a highly significant finding.

In particular, the 70 patients with a T/T genotype of rs353630 or the A/A genotype of rs684559 were estimated to have a median survival of 15 months after resection compared to 24 months for patients with protective genotypes.

The researchers note that, "The genotype of the identified SNPs can be determined before the initiation of any treatment by a technically straightforward blood test."

In fact, Dr. Grochola added, "Work is already under way to provide a commercially available genotyping assay for this biomarker signature to enable safe everyday use in the clinical practice."

In an accompanying editorial, Dr. John A. Windsor of the University of Auckland, New Zealand, observes, "The key decision, which will advance treatment, will be which combination of systemic treatments should be given to individual patients with PDAC, based on a panel of biomarkers that provide accurate data on expected biological behavior, including anticipated responsiveness to treatment."

"This," he writes, "is especially important as the vast biological heterogeneity of pancreatic adenocarcinoma comes into focus."

In an email to Reuters Health, Dr. Windsor further noted that many different biomarkers have been proposed, but "We have yet to find what we are looking for."


JAMA Surg 2019.

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