New 'lipidomics' method could bring fast cancer diagnosis

February 22, 2016

WEST LAFAYETTE, Ind. - Researchers have developed a new analytical tool for medical applications and biological research that might be used to diagnose cancer more rapidly than conventional methods.

The research has implications for the field of lipidomics, which involves the identification and quantification of cellular lipid molecules, how they interact with other components in cells and their role in biological systems.

"Lipidomics is a big field because changes of the lipid profile are related to the disease state or different stages of cells, so this is an important tool for either diagnostics or for systems biology," said Yu Xia, an associate professor in Purdue University's Department of Chemistry.

The new approach is the first to easily pinpoint the location of double bonds between carbon atoms in lipid molecules, allowing the identification of "isomers," a capability that could lead to the early diagnosis of cancer.

"The ratio of these isomers in normal tissue and tumor tissue can be different, significantly different," Xia said.

Research findings are detailed in a paper appearing online this week (Feb. 22) in Proceedings of the National Academy of Sciences.

"The location of double bonds is related to the biosynthetic pathway, or how the lipid was generated in your body, and this is related to the disease status and also the status of the cell biology," said Zheng Ouyang, a professor in Purdue's Weldon School of Biomedical Engineering, Department of Chemistry and School of Electrical and Computer Engineering.

The research paper was authored by postdoctoral research associate Xiaoxiao Ma; doctoral students Leelyn Chong and Ran Tian; Riyi Shi, a professor of neuroscience and biomedical engineering; Tony Y. Hu, an assistant professor of nanomedicine at the Houston Methodist Research Institute and the Weill Cornell Medical College of Cornell University; Ouyang; and Xia.

Lipids are important components of living cells and include fats, oils and waxes. They may exist as isomers, which have identical mass but possess subtle structural differences not easily detected by conventional analytical technologies. The new tool uses techniques called tandem mass spectrometry and the Paternò-Büchi reaction. In tandem mass spectrometry, charged molecules are fragmented into pieces, which are then measured and identified by their mass.

"Mass spec shows isomers as exactly the same molecular mass, so you are not able to see how much of which isomers are in tissue. But now we have a way to solve that problem," Ouyang said. "And we have found that the ratio of these isomers can be different between normal tissue and diseased tissue."

The researchers used a so-called "shotgun lipidomics" analysis enhanced by the Paternò-Büchi photochemical reaction, which modifies double bonds into rings that can then be easily cleaved into two parts. This allows the bonds to be measured and identified using mass spectrometry.

"Then we can derive the location of the double bond," Ouyang. "That's why this reaction is so important." The system was demonstrated with brain tissue from rats and also was applied to breast cancer tissue from mice. The researchers also used the method to study liver and kidney tissue and plan to include prostate cancer tissue in future research.

This method has two primary benefits.

"One is as a new tool for biologists, to relate the isomeric ratio to the system biology and cell biology," Ouyang said. "The second is to identify biomarkers for fast diagnosis of disease."

The method can be completed within hours, starting with small amounts of tissue -- tens of milligrams -- compared to weeks and hundreds of milligrams using conventional analytical techniques.

"More importantly, traditionally there has not been a good method for quickly distinguishing the unsaturated lipid isomers regardless of the amounts of tissue used," Ouyang said. "We believe that the research community may now use this approach to discover biomarkers and eventually apply it to diagnosis."

Although the research was conducted using a conventional laboratory mass spectrometer, the same operation could be carried out with a new miniature mass spectrometer. Whereas conventional mass spectrometers are relatively heavy, bulky instruments, Purdue researchers have recently developed miniature mass spectrometers, including the Mini 12, which weighs 40 pounds, is 12.5 inches wide and 16 inches high.

"Direct analysis using ambient sampling methods will further speed up the analysis process from hours to a minute," Ouyang said. "We want to apply this to imaging to study tissue, and we currently are integrating this method into miniature mass spectrometry systems. Eventually we hope to have biologists and medical professionals using it."

The system was used to identify 96 unsaturated fatty acids and glycerophospholipids in the brain tissue of rats, revealing that 50 percent of the lipids were mixtures of isomers characterized by the location of their carbon-carbon double bonds.

The researchers have filed a U.S. patent application on the technology through the Purdue Research Foundation's Office of Technology Commercialization. Ouyang is president of the company PURSPEC Technologies Inc., which is working to commercialize the analytical technology and the miniature mass spectrometer.
The research was funded by the National Science Foundation and the National Institutes of Health.

Writer: Emil Venere, 765-494-4709,

Sources: Yu Xia, 765-494-1142,

Zheng Ouyang, 765-494-2214,


Researchers have developed a new analytical tool for medical applications and biological research that might be used to diagnose cancer faster than conventional methods. From left are Purdue graduate student Leelyn Chong, postdoctoral research associate Xiaoxiao Ma, associate professor Yu Xia, professor Zheng Ouyang and professor Riyi Shi. (Purdue University image/Zheng Ouyang)

A publication-quality image is available at


Identi?cation and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction

Xiaoxiao Ma1,2,6, Leelyn Chong2,6, Ran Tian2,3, Riyi Shi2,3, Tony Y. Hu4,5, Zheng Ouyang2, and Yu Xia1

1Department of Chemistry, Purdue University, 2Weldon School of Biomedical Engineering, Purdue University, 3Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, 4Department of Nanomedicine, Houston Methodist Research Institute, 5Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 6These authors contributed equally to this work. To whom the correspondence should be addressed: Y. X. ( or Z. O. (

The ?eld of lipidomics has been signi?cantly advanced by mass spectrometric analysis. The distinction and quantitation of the unsaturated lipid isomers, however, remain as a long-standing challenge. In this study, we have developed an analytical tool for both identi?cation and quantitation of lipid C=C location isomers from complex mixtures using online Paternò-Büchi reaction coupled with tandem mass spectrometry (MS/MS). The potential of this method has been demonstrated with an implementation into shotgun lipid analysis of animal tissues. Among 96 of the unsaturated fatty acids and glycerophospholipids identi?ed from rat brain tissue, 50% of them were found as mixtures of C=C location isomers; and for the ?rst time, the quantitative information of lipid C=C isomers from a broad range of classes was obtained. This method also enabled facile cross-tissue examinations, which revealed signi?cant changes in C=C location isomer compositions of a series of FA and GP species between the normal and cancerous tissues.

Note to Journalists: A preprint of the research paper is available to journalists starting Wednesday, Feb. 17, on a secure reporters-only web site. Media may contact the PNAS News Office at or 202-334-1310. After the embargo has lifted, a copy of the research paper is available from Emil Venere, Purdue News Service, at 765-494-4709,

Purdue University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

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.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to