Fast-Affordable Blood Test Detects Cancer Before Symptoms Appear

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Fast-Affordable Blood Test Detects Cancer Before Symptoms Appear

Fast-Affordable Blood Test Detects Cancer Before Symptoms Appear

Researchers have developed a fast, cost-effective, and highly sensitive blood test to detect a clue protein produced by cancer cells.

This detection can identify a range of cancers before symptoms appear, potentially serving as a crucial tool for early disease diagnosis.

Many cancers often go undiagnosed until symptoms manifest, at which point the disease may have already spread and become challenging to treat.

Biomarkers are one method for cancer detection, but some biomarkers only emerge when cancer symptoms are present or are specific to certain cancer types.

In a new study, researchers at Rockefeller University have created a highly sensitive blood testing method capable of identifying a crucial protein produced by cancer cells, which has the potential for early detection in various cancer types.

LINE-1 ORF1p is a relatively new biomarker protein that has garnered attention in the scientific community. Long interspersed element-1 (LINE-1) is a retrotransposon, a virus-like element present in every human cell, which creates a new copy of itself by replicating and inserting into a new location in the genome. ORF1p is a high-level protein produced by LINE-1 in cancer, including esophageal cancer, colon cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, uterine cancer, pancreatic cancer, and head and neck cancers, among many of the most common and lethal cancers.

“Transposons are typically expressed during the process of sperm, egg, and embryo development, so in some cases, they have non-pathological biological expression,” said one of the co-authors of the study, John LaCava. “But apart from that, these ‘jumping genes’ remain silent in the genome because their activity can stress cells.”

In most cases, the body regulates LINE-1. However, when it expresses and produces ORF1p, it indicates that something may be amiss.

LaCava stated, “There are mechanisms to prevent LINE-1 expression and ORF1p production, so we can use the presence of this protein as a proxy for unhealthy cells that can no longer control their transcription. In other words, ORF1p should not be found in the blood of healthy individuals.”

It is well known that cancer cells begin to produce ORF1p in the early stages of the disease. Thus, finding an accurate method for detecting ORF1p means early cancer detection. Researchers set out to design a fast, low-cost test to detect ORF1p in plasma.

Due to the low concentration of ORF1p compared to traditional clinical laboratory methods’ detection limits, researchers used a single-molecule detection technology called Simoa, an ultra-sensitive immunoassay platform for measuring biomarkers in small volumes of serum, plasma, or cerebrospinal fluid. Custom nanobody reagents extracted from American camels were designed to detect and capture ORF1p protein.

“We developed these reagents to capture and describe molecular associations between ORF1p and other proteins in colorectal cancer,” LaCava said. “We know that most colorectal cancers have a lot of LINE-1 protein, so we infer that their interactions may dysregulate normal cell function in a way that benefits cancer. Separating LINE-1 particles allows us to observe these interactions up close.”

Fast-Affordable Blood Test Detects Cancer Before Symptoms Appear

Using the newly developed detection method, researchers investigated various cancer types and over 400 “healthy” control individuals who had no cancer at the time of blood donation. About 99% of the control group had no detectable ORF1p in their plasma, but among the five patients who tested positive for ORF1p, the one with the highest level of ORF1p in their plasma was diagnosed with advanced prostate cancer six months later. Among eight early-stage ovarian cancer patients in the cohort, four were ORF1p-positive, suggesting that this biomarker may indicate early-stage disease.

In summary, researchers found that the test exhibited high accuracy in detecting ORF1p in the blood samples of ovarian cancer, esophageal cancer, and colorectal cancer patients. Additionally, the cost of this test is under $3, and results can be obtained within two hours.

The primary author of this study, Martin Taylor, stated, “We are astounded by the effectiveness of this test across different cancer types.”

Apart from cancer detection, this test can also be used to assess the effectiveness of cancer treatments. If the treatment is successful, the patient’s ORF1p levels will decrease. Researchers studied 19 patients receiving treatment for esophageal cancer and found that among the 13 patients who responded to treatment, their ORF1p levels dropped below the assay’s detection limit.

Researchers envision incorporating this test into routine healthcare as an early warning system.

LaCava said, “When you’re healthy, you can measure your ORF1p levels to establish a baseline. Then, your doctor can closely monitor any spikes in ORF1p levels, indicating a change in your health. While there may be some minor fluctuations here and there, if a peak occurs, further investigation is needed.”

Further validation of this test method and determining whether it can detect cancers beyond cancer cells will require larger-scale cohort studies. Additionally, more research is needed to understand whether there is a normal baseline level of circulating ORF1p and what factors may affect this level.

This research was published in the journal “Cancer Discovery.”