Researchers identified an RNA biomarker that detected precancerous fallopian tube lesions with 92.3% sensitivity and 98.2% specificity in a validation cohort.
Researchers at Hoag Family Cancer Institute have identified a blood-based molecular signal that points to serous tubal intraepithelial carcinoma (STIC), an early precancerous stage of high-grade serous ovarian cancer. Hoag describes the finding as a world first. The work was published in Nature Medicine.
The finding adds to a broader trend toward molecular profiling in cancer diagnostics, as blood- and tissue-based signatures increasingly supplement imaging and histology.
Ovarian cancer is often diagnosed after the disease has spread. High-grade serous ovarian cancer often forms in the fallopian tube as STIC, a cluster of abnormal cells that are microscopic, noninvasive, and invisible to imaging and conventional cancer blood tests. STIC is usually found only incidentally during surgery to remove the fallopian tubes, the ovaries, or both.
Other groups are also exploring blood-based approaches to ovarian cancer screening, including an extracellular vesicle test aimed at earlier detection.
The study, led by Dr Rajan Gogna and Dr Esha Madan, found elevated blood levels of Tu-Stroma in women with both STIC and early-stage high-grade serous ovarian cancer. Tu-Stroma is an RNA molecule associated with the process by which cancer weakens neighboring healthy cells to make room for tumor growth. The researchers say the signal could potentially reveal cancer development years before conventional tests can detect a tumor.
The Hoag findings follow other recent progress on blood-based gynecologic cancer detection, including a multi-omics test designed to flag three gynecologic cancers at once.
“Ovarian cancer does not begin the day we discover a tumor. It often begins much earlier, with microscopic changes in the fallopian tubes that we can’t see during routine screenings,” says Gogna, director of translational research at the Hoag Family Cancer Institute, in a release.
Performance in a Validation Cohort
The eight-year, international, multi-institutional study drew on scientists and clinical samples from multiple countries to develop and validate the test. In a separate group of women used for validation, the test:
- Detected STIC in 92.3% of women who had it.
- Correctly identified 98.2% of healthy women.
The researchers also modeled performance in a high-risk population. In that model, about 72% of positive results would be accurate, while a negative result would be correct nearly 100% of the time.
The analysis used previously collected blood samples from women with confirmed diagnoses. It was not a prospective trial.
Next Steps and Clinical Implications
Hoag plans prospective clinical studies involving women from Hoag and the broader community, including those with and without elevated genetic risk of ovarian cancer. Researchers will collect blood samples and follow participants over time. They want to learn how early the signal can be detected, how reliably it identifies women with precursor disease, and whether it can help guide clinical decisions. The long-term goal is a clinically validated blood test for ovarian cancer surveillance and prevention.
The researchers say the test could be especially relevant for women with BRCA1 or BRCA2 mutations. These women often face decisions about preventive surgery to remove the fallopian tubes and ovaries, sometimes before completing their families and at the cost of early menopause.
Interpreting BRCA results already requires careful context; a recent study found family history remains essential to accurately gauge cancer risk from BRCA findings.
“Today, decisions about preventive surgery are largely guided by inherited risk, without knowing whether precancerous lesions are actually present. Our discovery could eventually provide that missing biological information,” says Madan, principal investigator and group leader of the Cell Competition in Tumor Microenvironment Laboratory at Hoag, in a release.
Madan adds that the team is working on approaches aimed at stopping these microscopic lesions from progressing. Further studies must validate the Tu-Stroma test before it can be used clinically.
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