Abstract

Abstract Backgrounds Adrenal cortical carcinoma (ACC) is a rare malignant tumor derived from the adrenal gland with a poor prognosis. Since there is no effective medical treatment, early diagnosis and surgical resection are the only way to cure ACC completely. However, early diagnosis of ACC is sometimes tricky because there are no useful diagnostic biomarkers to differentiate ACC from benign adrenal tumors. Therefore, we aimed to identify circulating protein biomarkers to distinguish malignant from benign adrenal tumors using mass spectrometry-based proteomic analysis. Methods Plasma samples were obtained from 27 patients with ACC and 69 age- and sex-matched patients with adrenal adenoma. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a data-independent acquisition (DIA) method in plasma samples. Among the quantified 381 proteins, differentially expressed proteins (DEPs) were selected using Student's t-tests for pairwise comparison with a false discovery rate < 0. 05 and |fold-change|> 1.5. In addition, we performed machine learning algorithms such as random forest and XGBoost to select featured DEPs to discriminate ACC. Results The mean age of patients was 52 years, and 38 (39.6%) patients were male. Among 19 DEPs, 8 proteins were overexpressed and 11 were underexpressed in ACC patients. In a further analysis using machine learning algorithms, random forest identified 4 proteins as important features for establishing the classifier. The panels with these four proteins showed a good discrimination performance with an area under the curve (AUC) of 0.94 and an accuracy of 0.96. Eight proteins were identified in the XGBoost algorithm. Four proteins in plasma samples were common DEPs from the traditional methods and machine learning algorithms. Conclusions High plasma levels of two proteins (One is involved in the migration, attachment and organization of cells into tissues. The other is V region of the variable domain of immunoglobulin light chains), and low plasma levels of two proteins (One is involved in cell-cell adhesion and recognition. The other is V region of the variable domain of immunoglobulin heavy chain) might be circulating protein biomarkers of ACCs compared with benign adrenal adenomas. Presentation: No date and time listed

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