Combining Genomics and Proteomics Yields Insights into Growth of Ovarian Cancer

Ovarian cancer reportedly accounts for 3% of all cancers in women and is the fifth leading cause of cancer deaths among women in the USA. In a new approach to resolving the factors that drive growth of ovarian cancer, investigators at Johns Hopkins University (Baltimore, MD, USA) and the Pacific Northwest National Laboratory (Richland, WA, USA) integrated proteomic measurements with published genomic data to yield a number of new insights into the disease.

The investigators performed comprehensive mass-spectrometry-based proteomic characterization of 169 high-grade serous carcinomas (HGSCs) that had been analyzed previously by The Cancer Genome Atlas (Bethesda, MD, USA), a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

Results published in the June 29, 2016, online edition of the journal Cell identified 9,600 proteins in all the tumors, among which were 3,586 proteins common to all 169 tumor samples. Alterations in segments of chromosomes 2, 7, 20, and 22 were shown to cause changes in abundance of more than 200 of these proteins. Many of those 200 proteins were found to be involved in cell movement and immune system function, processes implicated in cancer progression.

"Correlating our data with clinical outcomes is the first step toward the eventual ability to predict outcomes that reflect patient survival, with potential applications for precision medicine and new targets for pharmaceutical interventions," said contributing author Dr. Daniel W. Chan, professor of pathology and oncology at Johns Hopkins University. "With this knowledge, researchers expect to be better able to identify the biological factors defining the 70% of ovarian cancer patients who suffer from the most malignant form of ovarian cancer, called high-grade serous carcinoma. But just like anything in medicine, clinical validation will be a long and rigorous process."

"Historically, cancer has been looked at as a disease of the genome," said senior author Dr. Karin Rodland, chief scientist for biomedical research at the Pacific Northwest National Laboratory. "But that genome has to express itself in functional outcomes, and that is what the proteomic data add, because proteins are what get the actual work of the genome done. By comparing data for overlapping patient samples and finding comparable measurements of protein analysis at both institutions, we think our findings indicate excellent scientific rigor and reproducibility."

Related Links:
Johns Hopkins University
Pacific Northwest National Laboratory
The Cancer Genome Atlas