Abstract 1248P
Background
Despite recent progress, developing a low-cost and high-accuracy test for multi-cancer early detection (MCED) remains a challenge worldwide. Here, we report the development of a diagnostic model for MCED based on blood cell-free microRNAs (miRNA) using a training set composed of multiple cancer types.
Methods
We have previously assembled 3 large serum microarray datasets that assessed the expression of 2588 serum miRNAs from 6283 cancer patients (pts) across 13 cancer types and 5130 non-cancer controls, and developed a 4-miRNA model for MCED from a lung cancer training set ( Cancers 2022 ,14:1450). In the current study, an expanded training set including 1408 pts from 7 cancer types and 1408 age-, gender-matched non-cancer controls was compiled with the remaining participants organized into 3 validation sets. A new diagnostic model was built from the expanded training set by Linear Model for Microarray Data (limma) and 10-fold cross-validation.
Results
A new 4-miRNA diagnostic model was developed from the training set. In validation set 1 including 1358 lung cancer pts and 1501 non-cancer controls, the model achieved 99% sensitivity and 100% specificity. In validation set 2 comprising 1438 pts across 12 cancer types and 1623 non-cancer controls, the model achieved > 90% sensitivity for 8 cancer types and at least 75% sensitivity for 3 cancer types along with 99% specificity. In validation set 3 comprising 2079 pts across 4 cancer types and 598 non-cancer controls, the model achieved >90% sensitivity for all 4 cancer types and 98% specificity. Overall, the new model showed improved performance compared to the old model (p<0.001). Table: 1248P
Cancer type | N | Sensitivity of new model | Sensitivity of old model |
Validation set 2 | |||
Biliary Tract | 40 | 100% | 98% |
Bladder | 192 | 99% | 98% |
Breast | 135 | 1% | 0% |
Colorectal | 155 | 92% | 86% |
Esophageal | 124 | 91% | 85% |
Gastric | 150 | 100% | 100% |
Glioma | 40 | 98% | 88% |
Liver | 148 | 84% | 84% |
Ovarian | 133 | 79% | 62% |
Pancreatic | 149 | 91% | 83% |
Prostate | 40 | 98% | 92% |
Sarcoma | 132 | 75% | 72% |
Validation set 3 | |||
Gastric | 1067 | 100% | 100% |
Glioma | 196 | 96% | 87% |
Esophageal | 247 | 92% | 85% |
Prostate | 569 | 95% | 90% |
Conclusions
Our study provided further evidence in demonstrating that circulating miRNA-based diagnostic models have the potential to be developed into inexpensive, highly accurate and noninvasive tests for MCED. Models trained using multiple cancer types outperformed those trained from a single cancer type.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Hu: Financial Interests, Personal, Stocks or ownership: miRoncol Diagnostics. All other authors have declared no conflicts of interest.
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