Intercepting ovarian cancer at its earliest stage: validation of TU-stroma as a blood-based diagnostic biomarker

The National Cancer Institute awarded $541,081 to Hoag Memorial Hospital Presbyterian on September 3, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) for Project Grant R01CA318082.

The recipient will validate TU-STROMA, a long non-coding RNA biomarker detected in blood serum extracellular vesicles, as an early-stage ovarian cancer diagnostic. The work addresses the clinical need for blood-based detection of high-grade serous ovarian carcinoma (HGSC) at its earliest precursor stage, serous tubal intraepithelial carcinoma (STIC), when surgical intervention is most effective. Pilot data show TU-STROMA achieves AUC values approaching 0.99 in detecting STIC and early-stage HGSC and performs equally well in premenopausal women, a population where existing biomarkers (CA-125, HE4, ROMA) are unreliable. The validation will employ a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay on serum extracellular vesicles with locked thresholds using blinded, globally sourced cohorts spanning STIC, early-stage HGSC, and control samples. The team will test inter-laboratory reproducibility through distributed sample analysis and harmonized pipelines.

Performance occurs in Richmond, Virginia. The project runs through August 31, 2031.

Abstract

Ovarian cancer is the most lethal gynecologic malignancy, with high-grade serous ovarian carcinoma (hgsc) accounting for the majority of deaths and more than 450,000 women dying globally each year. The dismal survival rate stems from late diagnosis, as most women present only after peritoneal spread. Current blood tests such as CA-125, HE4, and roma are inadequate: they fail to detect pre-invasive disease, perform poorly in premenopausal women, and have not reduced mortality in clinical trials. There is therefore an urgent public health need for a blood test that can detect hgsc at its inception, when surgical intervention is most effective. Our work and that of others has established serous tubal intraepithelial carcinoma (stic) as the obligate precursor of hgsc, yet no existing biomarker captures this earliest window. We recently discovered TU-stroma, a long non-coding RNA secreted in extracellular vesicles that reprograms the surrounding stroma. This RNA appears in circulation at the stic stage, well before invasive cancer develops, and is mechanistically linked to tumor-stromal interactions. Pilot studies demonstrate that TU-stroma detects stic and early-stage hgsc with AUC values approaching 0.99 and performs equally well in premenopausal women, a group where CA-125 and HE4 are unreliable. This R01 will rigorously validate TU-stroma across blinded, globally sourced cohorts using a QRT-PCR assay on serum extracellular vesicles with locked thresholds to ensure reproducibility. Inter- laboratory reproducibility will be tested through distributed sample analysis and harmonized pipelines. Our team integrates expertise in ovarian cancer biology, molecular profiling, epigenetics, and statistical modeling, and has assembled a 600-sample training and validation set spanning stic, early-stage hgsc, and controls, with additional cohorts for external replication. The innovation is three-fold: first, TU-stroma is the only blood-based biomarker capable of detecting stic; second, IT provides reliable detection in premenopausal women, addressing a major unmet clinical need; and third, IT is mechanistically anchored, reflecting tumor-stromal fitness reprogramming rather than nonspecific tumor burden. Successful completion will deliver a clinically ready, inexpensive, and scalable test that can be deployed for high-risk brca or lynch carriers, symptomatic triage, and eventually population-level screening trials. The impact is transformative: shifting hgsc diagnosis from late- stage to pre-invasive disease, enabling risk-reducing surgery at the right time, and preventing thousands of deaths each year. By bridging fundamental biology with rigorous clinical validation, this project will establish a new paradigm for ovarian cancer early detection and cancer interception.