Can a Prognostic Gene-Expression Signature Predict Survival in Ovarian Cancer?
Posted: Tuesday, September 1, 2020
Joshua Millstein, PhD, of the Keck School of Medicine, University of Southern California (USC), Los Angeles, and a host of multinational colleagues developed a 101-gene expression signature to identify patients with high-grade serous ovarian cancer who might benefit from clinical trial participation. The findings, which were published in the Annals of Oncology, may aid in the development of targeted therapies.
“At the moment, the majority of ovarian cancer patients get the same treatment,” commented senior author Susan J. Ramus, PhD, of the University of New South Wales, Sydney, in a USC press release. “[This gene-expression signature] is a way to stratify patients and potentially give more personalized treatment down the track.”
Pretreatment formalin-fixed paraffin-embedded tumor samples from 4,071 women diagnosed with high-grade serous ovarian cancer were obtained. An individual participant meta-analysis of 6 transcriptome-wide microarray studies identified 513 candidate prognostic genes. Using quality-controlled samples provided by 3,769 patients, the investigators applied NanoString technology to measure gene expression. A prognostic model for 5-year overall survival was developed by elastic net regularization.
Based on the results of covariate-adjusted single-gene analyses, the expression levels of 276 genes seemed to be associated with overall survival (false discovery rate < .05); TAP1, ZFHX4, CXCL9, FBN1, and PTGER3 were the top five genes (P < .001). The prognostic signature of 101 genes in addition to age and stage seemed to perform better than age and stage alone. According to the investigators, the gain of one standard deviation in the gene-expression score corresponded with a greater than twofold increase in the risk of death (P < .001). The median survival by gene-expression score quintile was determined: 9.5 years in the lowest quintile; 5.4 years in the second quintile; 3.8 years in the third quintile; 3.2 years in the fourth quintile; and 2.3 years in the highest quintile.
Disclosure: For full disclosures of the study authors, visit annalsofoncology.org.