Ovarian cancer, one of the most difficult to diagnose and treat, is especially lethal for that reason, but University of California, San Diego School of Medicine and Moores Cancer Center researchers have found biomarkers they believe could be used to diagnose the disease at an early stage.
The researchers identified six Messenger RNA isoforms (bits of genetic material that have similar but not identical amino acid sequences and code for functionally similar proteins) that are produced by ovarian cancer cells — but not normal cells. Their presence could indicate early ovarian cancer, according to a study published the week of May 25 in the Proceedings of the National Academy of Sciences.
And several of the mRNA isoforms code for unique proteins that could be targeted with new therapeutic treatments.
“We were inspired by many studies aimed at using DNA to detect cancer,” said lead author Christian Barrett, bioinformatics expert and project scientist in the UC San Diego School of Medicine Institute for Genomic Medicine.
“But we wondered if we could instead develop an ovarian cancer detection test based on tumor-specific mRNA that has disseminated from cancer cells to the cervix and can be collected during a routine Pap test,” Barrett said in a press release May 25.
DNA, the blueprint for life, contains much more information than just the genes that code for proteins. In contrast, mRNAs, are complementary copies of just the genes. They carry the instructions for every protein that the cell will produce “from the nucleus to the cytoplasm, where cellular machinery can read the recipe and build the corresponding proteins,” the press release said.
According to the study’s authors, the advantage of using cancer mRNA for diagnosis rather than DNA is “the sheer numbers” — a cancer cell might have just one to a few copies of a DNA mutation, but mRNA variants can occur in hundreds to thousands of copies in each cell.
The research team developed an algorithm to explore two large public genetic databases, The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) program, both sponsored by the National Institutes of Health
TCGA is a catalog of RNA and DNA from 500 tumors including many types of cancer, and GTEx is a database of RNA and DNA from normal tissues. The researchers were able to analyze mRNA sequences from 296 ovarian cancers and 1,839 normal tissue samples.
The researchers found six mRNA isoform molecules that have the tumor specificity required for an early detection diagnostic of ovarian cancer.
“Our experimental findings were made in a laboratory and were performed on ovarian cancer cells from cell lines,” said study co-author Dr. Cheryl Saenz, clinical professor of reproductive medicine who specializes in treating gynecologic cancers. “Clinical trials will need to be conducted on women to confirm the presence of these markers in women that we know have cancer, as well as to document the absence of the markers in women that do not have ovarian cancer.”
The authors acknowledge limitations in their approach, including “technical limitations in detecting mRNA isoforms, a shortage of normal ovarian and fallopian tube control samples and the possibility that tumor cells that disseminate to the cervix may not genetically act the same as the primary tumor.”
Yet results are so promising the researchers recommend expanding their process for identifying tumor-specific mRNA isoforms to other tumor types.