Prediction of tissue-of-origin of early-stage cancers using serum miRNomes
Menée à partir de 7 931 échantillons sériques prélevés sur des patients atteints d'une tumeur solide et 5 013 échantillons sériques prélevés sur des témoins sains, cette étude met en évidence l'intérêt des microARNs en combinaison avec l'intelligence artificielle pour détecter précocement un cancer et déterminer avec précision sa localisation
Background : Non-invasive detection of early-stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively.
Methods : A serum miRNome-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7,931 serum samples from patients with 13 types of solid cancers and 5,013 non-cancer samples. The validation set consisted of 1,990 cancer and 1,256 non-cancer samples. The contribution of each miRNA to the cancer-type classification was evaluated and those with a high contribution were identified.
Results : Cancer type was predicted with an accuracy of 0.88 (95% CI, 0.87–0.90) in all stages and an accuracy of 0.90 (95% CI, 0.88–0.91) in resectable stages (Stages 0–II). The F1-score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type-specific serum miRNomes.
Conclusions : This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.
JNCI Cancer Spectrum , article en libre accès, 2021