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Purpose: To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs)., Methods: We retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect., Results: There was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P>0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities., Conclusions: The radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Fan, Shan, Zhou, Pang, Fu, Yang, Wu, Sun, Yang and Huang.)