Proteogenomics: A Novel Method To Study Biologic Factors of Ovarian Cancer

Proteogenomics: A Novel Method To Study Biologic Factors of Ovarian Cancer

A recent study led by researchers at the Pacific Northwest National Laboratory (PNNL) and Johns Hopkins Medical Institutions (JHMI) demonstrated the usefulness of combining genomic and proteomic data known as proteogenomics to gain new insights about biological factors responsible for ovarian cancer.

Results from the study, “Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer,” were published in Cell.

Though some progress has been made in the fight against ovarian cancer, the underlying mechanisms are still not fully understood. This is particularly related to the lack of suitably advanced analysis methods capable of providing a full view of the disease governing mechanisms.

Researchers developed a promising novel method based on the combination of genomics and proteomics: proteogenomics, a powerful method to gain insights into the development and progress of the most malignant forms of ovarian cancer.

“Historically, cancer’s been looked at as a disease of the genome,” Karin Rodland, a senior author of the study and chief scientist for biomedical research at PNNL, said in a press release. “But that genome has to express itself in functional outcomes, and that’s what the proteomic data adds, because proteins do the actual work of the genome.”

Daniel W. Chan, the study’s other senior author, who led the team at Johns Hopkins  said: “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. But just like anything in medicine, clinical validation will be a long and rigorous process.”

The researchers analyzed tumor tissues from 169 patients with high-grade serous carcinoma, the most malignant form of ovarian cancer. The genomic and clinical data were retrieved from Cancer Genome Atlas (TCGA) and among the samples, 122 of them were selected for further analysis due to their capability to repair damaged DNA.

“We chose to examine these samples because patients with changes in these genes already are benefiting from a specific drug regimen for breast cancer, so if we could find similar changes in ovarian cancer genomes and proteomes, those patients would likely benefit from the same regimen,” said Chan, a professor of pathology and oncology at JHU.

“We examined the data for the shortest-surviving patients and the longest-surviving patients hoping to pinpoint biological factors associated with extremely short survival or better-than-average, longer survival,” Rodland said.

The collaboration between PNNL and JHMI researchers led to proteogenomic, which allowed them to identify 9,600 proteins of which 3,586 were common to the 169 tumor samples.

Using this method, the researchers expect to gain an in-depth understanding of the biological factors responsible for most aggressive ovarian cancers, like high-grade serous carcinoma.

“Adding the information about the proteome on top of the genome provides an entirely new dimension of information that has enabled the discovery of new biological insights to ovarian cancer, while creating a valuable resource that the scientific community can use to generate new hypotheses about the disease, and how to treat it,” Rodland said.