Researchers from Mass General Brigham, the Wyss Institute for Biologically Inspired Engineering at Harvard University, and Dana-Farber Cancer Institute, in collaboration with researchers from across the country and beyond the U.S., developed an affordable, highly sensitive blood test that detects trace amounts of the cancer biomarker LINE-1 ORF1p with strong specificity for several prevalent cancer types.

The human transposon-derived protein 'LINE-1 ORF1p' has potential in tissue diagnostics and cancer treatment, potentially providing precise biomarkers for certain cancer types.

This test requires merely half a drop of blood (25 microliters) for each analysis. The tool exhibits promise for early cancer detection and disease monitoring and can potentially complement other tools for detecting, stratifying risk, and treating cancer. The results have been published in Cancer Discovery.

Advancement in Cancer Biomarker Detection Research

"Cancer biomarker detection is a burgeoning area of research and is still a young field," said co-corresponding author David Walt, Ph.D., of the Department of Pathology at Brigham and Women's Hospital, a founding member of Mass General Brigham. Walt holds a core faculty position at the Wyss Institute as well.

The Walt lab developed a single-molecule-based detection technology known as SIMOA, which the new study utilizes. This test aims to identify the open reading frame 1 protein (ORF1p), a transposable element protein present in many cancers but absent in corresponding normal tissue, indicating a high risk of cancer lethality.

Researchers have been searching for a sensitive and accurate ORF1p detection test for a long time. The authors conducted their initial investigation of the test as a pilot experiment, and it exceeded their expectations. Subsequently, they made a series of engineering improvements and conducted multiple iterations using patient samples.

"We were shocked by how well this test worked in detecting the biomarker's expression across cancer types," said lead author Martin Taylor, M.D., Ph.D., of the Department of Pathology at Massachusetts General Hospital, the other founding member of Mass General Brigham. "It's created more questions for us to explore and sparked interest among collaborators across many institutions."

The researchers collaborated with investigators from Mass General Brigham, Dana-Farber, Beth Israel Deaconess, and MIT in Boston, as well as from Rockefeller University, University of Pennsylvania, University of Washington (Seattle), Johns Hopkins, Groningen (Netherlands), and Canon Medical. Together, they conducted tests on blood samples from patients with various cancer types, such as ovarian and colorectal cancer.

Researchers have developed an ultrasensitive assessment tool that accurately measures ORF1p levels in blood samples of cancer patients, confirming its specificity for cancer detection. The tool was found to be prevalent in carcinomas and high-risk precursor lesions in tissue samples from 200 colon cancer and 75 esophageal biopsies.

"Pervasive expression of ORF1p in carcinomas and the lack of expression in normal tissues makes ORF1p unlike other protein biomarkers, which have normal expression levels. This unique biology makes it highly specific," said Taylor.

One limitation of the study is that it doesn't offer essential information, like the precise location of cancerous tissues in the body. Furthermore, the ultrasensitive assessment tool doesn't effectively identify all cancer types and their subcategories. The team foresees the tool's potential as a complementary addition to other tests to enhance early detection methods. It could also enable doctors to continuously monitor a patient's response to cancer therapy and make real-time adjustments when necessary.

"The test is very specific, but it doesn't tell us enough information to be used in a vacuum," said Walt. "It's exciting to see the early success of this ultrasensitive assessment tool, but there is more work to be done."

The pathology researchers from the study are currently collaborating with clinicians to assess the test's accuracy in larger trial cohorts and diverse patient populations. They aim to determine the potential usefulness of the ORF1p biomarker in patient care. Additionally, they are actively investigating whether this biomarker can be employed to stratify the cancer risk in patients.

"We've known since the 1980s that transposable elements were active in some cancers, and nearly 10 years ago we reported that ORF1p was a pervasive cancer biomarker, but, until now, we haven't had the ability to detect it in blood tests," said co-corresponding author Kathleen Burns, M.D., Ph.D., Chair of the Department of Pathology at Dana-Farber.

Faber added "Having a technology capable of detecting ORF1p in blood opens so many possibilities for clinical applications. We were fortunate to assemble this tremendous team to push the limits of these assays and obtain and test these precious samples. There's a lot of excitement as our work continues."