Noninvasive multi-cancer detection using blood-based cell-free microRNAs

Sep 21, 2026

Uploaded by Miles

Early-stage cancer patients generally have better survival, yet effective population-level screening remains limited for many cancer types. This study develops a miRNA-based blood test for multi-cancer early detection using serum microRNA microarray data from cancer patients and matched controls. A 4-microRNA diagnostic model was trained on 1,408 patients from 7 cancer types and validated across three independent cohorts totaling 4,875 cancer patients from 13 types and 3,722 controls, achieving high sensitivity and >99% specificity.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Participants and datasets

Results

Participants and datasets

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Noninvasive multi-cancer detection using blood-based cell-free microRNAs Jason Zhang1, Hallgeir Rui2 & Hai Hu3,4􀀍 Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age-and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of 4,875 cancer patients across 13 cancer types and 3,722 non-cancer participants, the 4-microRNA model achieved greater than 90% sensitivity for 9 cancer types (lung, biliary tract, bladder, colorectal, esophageal, gastric, glioma, pancreatic, and prostate cancers) and 75–84% sensitivity for 3 cancer types (sarcoma, liver, and ovarian cancer), while maintaining greater than 99% specificity. The sensitivity remained to be > 99% for patients with stage 1 lung cancer. Our study provided novel evidence to support the development of an inexpensive and accurate miRNA-based blood test for multi-cancer early detection. Keywords Multi-cancer early detection, MicroRNA, Noninvasive, Blood-based diagnostic model Cancer ranks the first or second leading cause of death in most countries worldwide1. In the United States, the American Cancer Society estimated 1.9 million new cancer cases and nearly 610 K cancer deaths in 20222. Patients diagnosed with early-stage cancers have much higher survival rates than those at late stages. For example, the 5-year patient survival rate for localized colorectal cancers is 91% but only 15% for those that have spread to distant organs2. However, early-stage cancer patients often have no symptoms and thus are more likely to miss timely diagnosis3,4. Therefore, detecting cancers at early stages is paramount to reduce cancer-related mortality. The most effective way for detecting cancer early is the availability and accessibility of cancer screening tools for the general population. Unfortunately, the options of such screening tools are limited. Currently, only four cancer types have screening tests recommended by the United States Preventive Service Task Force (USPSTF): mammography for breast cancer, cytology/HPV testing for cervical cancer, colonoscopy and/or stool-based testing for colon cancer, and low-dose CT scans for lung cancer5–8. A challenge of using these single cancer-based screening tests is that when used sequentially, they could lead to dramatically increased cumulative incidence of false positives9. Therefore, a low cost, high performance and noninvasive test that can detect multiple cancers simultaneously will overcome the pitfalls of these single cancer-based screening tools and greatly facilitate the adoption and increase the compliance of the so-called multi-cancer early detection (MCED) in high-risk general population. Here we report the development of a circulating microRNA (miRNA)-based MCED model using a multicancer training set and show its validation in a broader cohort of patients and controls, demonstrating a high accuracy of detecting 12 cancer types. Results Participants and datasets To develop a MCED model, we identified eight serum miRNA microarray datasets from Gene Expression Omnibus (GEO)10, 11, which included data from 13 cancer types (biliary tract, bladder, breast, colorectal, esophageal, gastric, glioma, liver, lung, ovarian, pancreatic, prostate, sarcoma) and were all generated from the 1Del Norte High School, San Diego, CA, USA. 2Department of Pharmacology, Physiology & Cancer Bi

FAQs

What is the main goal of this study?

To develop and validate a noninvasive blood test based on circulating cell-free microRNAs for early detection of multiple cancer types.

How was the diagnostic model trained and tested?

The model was trained using a large multi-cancer training set (1,408 patients across 7 cancer types) and evaluated with three independent validation sets covering 13 cancer types and matched non-cancer participants.

How does performance vary across cancer types?

The 4-microRNA model achieved >90% sensitivity for 9 cancer types and 75–84% sensitivity for 3 cancer types, while maintaining >99% specificity and very high sensitivity for stage 1 lung cancer.

Sep 21, 2026

Uploaded by Miles

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