In JNCI cancer spectrum
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.
Matsuzaki Juntaro, Kato Ken, Oono Kenta, Tsuchiya Naoto, Sudo Kazuki, Shimomura Akihiko, Tamura Kenji, Shiino Sho, Kinoshita Takayuki, Daiko Hiroyuki, Wada Takeyuki, Katai Hitoshi, Ochiai Hiroki, Kanemitsu Yukihide, Takamaru Hiroyuki, Abe Seiichiro, Saito Yutaka, Boku Narikazu, Kondo Shunsuke, Ueno Hideki, Okusaka Takuji, Shimada Kazuaki, Ohe Yuichiro, Asakura Keisuke, Yoshida Yukihiro, Watanabe Shun-Ichi, Asano Naofumi, Kawai Akira, Ohno Makoto, Narita Yoshitaka, Ishikawa Mitsuya, Kato Tomoyasu, Fujimoto Hiroyuki, Niida Shumpei, Sakamoto Hiromi, Takizawa Satoko, Akiba Takuya, Okanohara Daisuke, Shiraishi Kouya, Kohno Takashi, Takeshita Fumitaka, Nakagama Hitoshi, Ota Nobuyuki, Ochiya Takahiro
2022-Nov-25
early detection, microRNA, transfer learning
