Most random gene expression signatures are significantly associated with breast cancer outcome, according to a research team at Universit Libre de Bruxelles.

The Belgian group, which presented its work in PLoS Computational Biology last year, compared 48 published breast cancer outcome signatures to those comprising random genes and found that 28 of the breast cancer signatures, or 60 percent, were "not significantly better outcome predictors than random signatures of identical size," while 11, or 23 percent, were actually poorer predictors than the median random signature.

These findings prompted a review that appeared in Bioessays this month, as well as a commentary published in June in the journal Breast Cancer Research.

Bertrand Jordan, author of the Bioessays review, called the paper "provocative and iconoclastic," as it "states that many published interpretations of expression profiling experiments are not really significant."

Jordan, who is an emeritus research director at the French National Center for Scientific Research, told BioArray News this week that the paper makes a "strong statement" that "seems to be backed by fairly solid data" and "deserved more exposure than it had received" initially.

In addition to the review and commentary, Vincent Detours, a computational biologist at ULB and corresponding author on the PLoS Computational Biology paper, said that he has received "encouragement" from other researchers since it first appeared.

"My impression is that many people were aware of the issue or felt uncomfortable about the proliferation of signatures, and were pleased to see their concerns addressed," Detours told BioArray News last week.

An 'Iconoclastic' Paper

As Detours noted in an opinion article published last December in The Scientist, the accumulation of signatures with all sorts of biological meaning, but nearly identical prognostic values, had "already looked suspicious" to him, coauthors David Venet and Jacques Dumont, and others as far back as 2007.

After collecting from the literature some signatures with as little connection to cancer as possible, the authors discovered that the signature of the blood cells of Japanese patients who were told jokes after lunch, and a signature derived from the microarray analysis of the brains from mice that suffered social defeat were both associated with breast cancer outcome by any statistical standards.

Link:
'Provocative' Paper Sparks Debate on Relevance of Breast Cancer Gene Expression Signatures

Comments are closed.