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

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.