Scientists are actively investigating specific elements within our DNA, as well as cells and molecules, that may indicate the presence of
. While some progress has been made in identifying these markers in the bloodstream, it remains a complex task to do so accurately and cost-effectively for routine screening.
Researchers at Rockefeller University, in collaboration with an international team, have developed a blood test capable of pinpointing a crucial protein produced by
While most proteins in our body can be detected through tests for CA125 and HE4, these methods are inadequate for reliably determining whether an individual has cancer, as they may also be present in healthy tissues.
The scientists focused their efforts on a protein called ORF1p, which is generated by a specific genetic component in our DNA known as L1. The researchers noted that ORF1p is frequently found in various types of cancer, particularly those in which a vital gene called p53 is dysfunctional. These types of cancer are prevalent and can pose significant risks.
According to John LaCava, a co-author of the study and a research associate at Rockefeller, “ORF1p shouldn’t be detectable in the bloodstream of a healthy individual.”
What’s particularly intriguing is that ORF1p is produced in significant quantities even before cancer becomes visible under a microscope. Standard laboratory tests are unable to detect it. To overcome this challenge, the researchers employed an exceptionally sensitive technology known as Single Molecule Arrays (Simoa), capable of identifying ORF1p at exceedingly low levels in the blood.
Michael P. Rout, the head of the Rockefeller lab, stated, “The assay has groundbreaking potential as an early diagnostic test for lethal cancers.” He believes that such ultra-sensitive detection tools have the potential to revolutionize patient outcomes.
In initial tests, the team detected ORF1p protein in patients with advanced breast and colorectal cancers, even in minuscule amounts, thanks to Simoa. The researchers also examined the plasma of 400 healthy individuals spanning ages 20 to 90.
According to the press release, ORF1p was undetectable in 97-99% of them. Out of the five individuals who exhibited noticeable levels of ORF1p, the one with the highest concentration was subsequently diagnosed with advanced prostate cancer six months after the initial test.
The study, recently published in Cancer Discovery, underscores the need for improved biomarkers in early cancer detection, risk assessment, treatment selection, and treatment response monitoring. ORF1p, with its minimal expression in normal tissues and elevated levels in carcinomas and high-risk precursors, emerges as a promising, highly specific cancer biomarker.
Use of Advanced Digital Immunoassays to Detect Cancer
Advanced digital immunoassays were engineered to detect ORF1p concentrations in plasma at astonishingly low levels, down to mid-attomolar (10-17 M). These assays exhibited high specificity across multiple cancers, showing potential for early ovarian cancer detection, enhancing diagnostic performance in a multi-analyte panel, enabling early therapeutic response monitoring in gastroesophageal cancers, and offering prognostic value for overall survival in gastroesophageal and colorectal cancers.
Collectively, these findings position ORF1p as a versatile biomarker for various cancers, with potential applications in disease detection and monitoring.
- Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker – (https:aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0313/729035/Ultrasensitive-detection-of-circulating-LINE-1)
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