Nav: Home

Researchers isolate possible ovarian cancer biomarkers

September 16, 2015

Researchers from North Carolina State University utilized a highly sensitive mass spectrometry analysis to identify and measure difficult-to-detect N-glycan biomarkers associated with ovarian cancers in stages I - IV. In a surprising finding, the researchers determined that the level of biomarkers associated with ovarian cancer does not simply increase or decrease over the course of the disease, but can rise and fall during different stages. These findings have implications for our understanding of, as well as diagnostic and therapeutic approaches to, ovarian cancer.

Ovarian cancer has a high mortality rate, primarily because the disease is difficult to detect in its early stages. The majority of diagnoses - over 80 percent - occur in the late stage, and 70 percent of those cases will be fatal. Scientists know that ovarian cancer metastasis is associated with errors in glycosylation, the process by which a sugar chain attaches to a protein at a specific amino acid. The glycans, or sugar chains, affect a number of cellular processes, and it is difficult to measure differences between normal and cancer-associated glycans in order to determine whether or not they are useful as biomarkers for the disease.

David Muddiman, the Jacob and Betty Belin Distinguished Professor of Chemistry at NC State and corresponding author of a paper describing the work, along with Ph.D. candidate and lead author Elizabeth Hecht and other NC State colleagues, wanted to see if it was possible to measure differences between normal and cancer-associated glycans and identify cancer biomarkers. They obtained 164 blood samples from female patients at the Mayo Clinic: 82 from women who were diagnosed with ovarian cancer, and 82 from cancer-free female patients.

Muddiman and Hecht isolated N-glycans (glycans that attach to proteins at the amino acid asparagine) from the patients' plasma and prepared them for analysis with mass spectrometry by labeling them with hydrophobic tags specifically designed to enhance the sensitivity of the test. Their method of hydrophobic tagging, known as Individuality Normalization when Labeling with Glycan Hydrazide Tags, or INLIGHT, makes it easier for the glycans to move into a gas phase where the mass spectrometer can "see" them better. Furthermore, by labeling the control and cancer plasma samples with two similar but chemically unique tags, highly accurate measurements could be obtained.

The mass spectrometry results were put into statistical models to determine changes in glycan levels between the control patients and those with cancer. The researchers identified seven N-glycans with different chemical compositions that were statistically significant enough to be considered possible biomarkers.

"This was the first time we had used our INLIGHT strategy with biological samples," says Hecht. "Our testing was sensitive enough to detect differences between the samples that were as low as 17 percent. Most testing can only detect two-fold changes, or a 100 percent increase. So we've been able to demonstrate that it is possible to detect and study, to a fine level of detail, a very hard-to-detect molecule - and that this molecule may be useful as a biomarker for ovarian cancer."

The researchers also found that numbers of cancer associated N-glycans did not remain constant over the course of the disease, but could vary from stage to stage.

"It seems that our usual and often unstated assumption about the process of disease - that what we use to measure disease progression should either consistently increase or decrease during the course of the illness - is incorrect," says Muddiman. "The molecular signature of cancer is not a one-way street."

The research appears in the Journal of Proteome Research. NC State statistics professor Alison Motsinger-Reif, bioinformatics analyst Elizabeth Scholl, former doctoral student Hunter Walker, former undergraduate student Amber Taylor, and Dr. William Cliby from the Mayo Clinic also contributed to the work. Funding was provided by the National Institutes of Health (NIH NCI IMAT grant R33 CA147988-02, NIGMS grant T32GM008776) and the W.M. Keck Foundation.
-end-
Note to editors: Abstract follows

"Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples"

DOI: 10.1021/acs.jproteome.5b00703

Authors: Elizabeth Hecht, Elizabeth Scholl, Hunter Walker, Amber Taylor, Alison Motsinger-Reif, David Muddiman, NC State University; William Cliby, Mayo Clinic

Published: Online in the Journal of Proteome Research

Abstract: An early-stage, population-wide, biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. For relative quantitation, glycans were analyzed by the Individuality Normalization when Labeling with Glycan Hydrazide Tags (INLIGHTTM) strategy for enhanced electrospray ionization, MS/MS analysis. 63 glycan cancer burden ratios (GBRs), defined as the log10-ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after FDR correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response.

North Carolina State University

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.