NEW YORK (360Dx) – Scientists at Japanese multinational technology firm Hitachi have developed a new approach for diagnosing cancer based on using urinary metabolites as biomarkers. The company is now commencing a trial of the test platform in 250 patients to generate more data while it considers how to best commercialize it.
"We have been conducting basic research to construct cancer test models using urinary metabolites for several types of cancers for several years," said Minoru Sakairi, chief scientist at Hitachi's Center for Exploratory Research in Tokyo, which is managed through its Research & Development Group. "We are now accumulating clinical data to prove that these models are reasonable."
According to Sakairi, Hitachi in 2015 began looking into using urinary metabolites as biomarkers for cancer testing within the center. "Urine plays a major role in regulating the water volume in the body and in the excretion of waste products from the blood," noted Sakairi. Since the small molecules are generated when nutrients are consumed, their quantities fluctuate depending on the health of the individual.
This principle underlies the concept of Hitachi's test. Based on the presence of various metabolites in a patient's urine, the company aims to be able to determine whether the person has cancer. The first two indications that will be studied as part of the current trial are colorectal cancer and breast cancer. Should the trial be successful, Hitachi imagines that such an approach could be implemented in the future to improve cancer testing across Japan by making it possible for people to test themselves.
"We believe that it's possible to develop a system where patients collect their urine samples at home and then send them to a testing center for analysis," said Sakairi. He added that such a system would be "effective in a country like Japan where there are more than a million cancer patients and the consultation rate for precision cancer testing is low compared with other Organization for Economic Co-operation and Development countries."
Hitachi was inspired in part by a 2015 OECD report that showed Japanese cancer screening programs lagging other member states. Roughly 80 percent of women aged 50 to 59 in the US are screened for breast cancer, the report noted, compared to about 41 percent in Japan.
Hitachi's approach relies on liquid chromatography/mass spectrometry to quantitatively analyze patients' urine for biomarkers linked to cancer. The researchers previously analyzed urine samples from cancer patients and healthy individuals, and "believe that important biomarker candidates for several cancer types could be extracted by using our method," Sakairi said. More specifically, the researchers used heat map and principal component analysis of metabolites to select candidate biomarkers that differentiated those with cancer from healthy individuals. The company discussed the findings in a July 2016 statement, noting they had identified about 10 candidate markers from around 1,300 urinary metabolites.
Some of the work was funded through Japan's Agency for Medical Research and Development.
Sakairi noted that LC/MS, as well as capillary electrophoresis mass spectrometry, has been employed in metabolomic studies in the past, but said that the "overwhelming majority" of these studies have been applied to blood samples. "These methods have not been fully investigated for efficient extraction of biomarker candidates from urinary metabolites," he said.
A number of firms are engaged in delivering urine-based cancer tests to market, though based on DNA markers rather than metabolites. Earlier this year, Nanomed Diagnostics, a spinout of the University of Twente in the Netherlands announced plans to develop a nanotechnology platform that could diagnose a variety of cancers – including lung, bladder, cervical, and colon cancer – based on DNA methylation markers obtained from urine samples. In January, Denmark's Genomic Expression received a €3.7 million ($4.2 million) EU Horizon 2020 grant to advance a urine-based test for bladder cancer. Other companies, such as the UK's Acris Biotechnology and Dutch diagnostics firm MdxHealth, have developed urine-based tests for prostate cancer.
According to Sakairi, Hitachi is now working with researchers at Nagoya University to carry out the current trial. While the trial is set to wrap up by the end of this year, it's unclear when the test method could be commercialized in Japan or elsewhere. Sakairi said that Hitachi is currently discussing how to make the test available, but has not yet reached a decision.
In the meantime, Sakairi's group aims to continue its search for biomarkers and will continue to accumulate more clinical data. "Ultimately, our aim is to establish a diagnostic method using multiple biomarkers extracting from urinary metabolites rather than a single biomarker," said Sakairi. "Providing the tests are performed using LC/MS, the cost of analysis using multiple biomarkers will be almost similar to that using a single biomarker," he claimed.
Sakaira's group has not yet described the new approach in a publication. However, he said that it has prepared several papers with colleagues at Nagoya University Hospital. He did publish a review article on Hitachi's work last year, in which he discussed the use of the approach in breast and colon cancer cases.
Sakairi said that Hitachi has been encouraged in its efforts by recent research into cancer testing using urine, particularly by other groups in Japan. A Japanese research team unaffiliated with Hitachi showed in a 2015 British Journal of Cancer study that polyamine N1, N12-diacetylspermine could be used as a urinary marker for the diagnosis and prognosis of non-small-cell lung cancer.
He also noted that scientists at the Japan Agency for Medical Research and Development have been investigating the use of nanowire methods for detecting cancer-related microRNAs in urine.
Scientists at Kyushu University have also reported the use of nematodes to detect cancer based on urine samples from patients. The work was profiled in a 2015 PLoS One study. In 2017, Hitachi partnered with HirotsuBio, a Kyushu University venture company, to commercialize the method.
"This method uses the attraction of nematodes to urine from cancer patients and their avoidance of urine from healthy individuals, and clinical data are currently being collected," said Sakairi. He said that another research team at Hitachi is engaged in the partnership.