<i>CDH2</i> and <i>CDH13</i> as potential prognostic and therapeutic targets for adrenocortical carcinoma

Cadherin 2 (CDH2, N-cadherin) and cadherin 13 (CDH13, T-cadherin, H-cadherin) affect the progress and prognoses of many cancers. However, their roles in adrenocortical carcinoma (ACC), a rare endocrine cancer, remain unclear. To decipher the roles of these proteins in ACC and to identify their regulatory targets, we analyzed their expression levels, gene regulatory networks, prognostic value, and targets in ACC, using various bioinformatic analyses. <i>CDH2</i> was strongly downregulated and <i>CDH13</i> was strongly upregulated in patients with ACC; the expression levels of these genes affected the prognosis. In 75 patients, the expression of <i>CDH2</i> and <i>CDH13</i> was altered by 8% and 5%, respectively. <i>CDH2</i> and <i>CDH13</i>, as well as their neighboring genes, were predicted to form a complex network of interactions, mainly through coexpression and physical and genetic interactions. <i>CDH2</i> and its altered neighboring genes (ANGs) mainly affect tumor-related gene expression, cell cycle, and energy metabolism. The regulation of tumor-related integrin function, gene transcription, metabolism, and amide and phospholipid metabolism are the main functions of <i>CDH13</i> and its ANGs. MiRNA and kinase targets of <i>CDH2</i> and <i>CDH13</i> in ACC were identified. <i>CDH13</i> expression in patients with ACC was positively associated with immune cell infiltration. Anti-PD1/CTLA-4/PD-L1 immunotherapy significantly downregulated the expression of <i>CDH13</i> in patients with ACC. Foretinib and elesclomol were predicted to exert strong inhibitory effects on SW13 cells by inhibiting the expression of <i>CDH2</i> and <i>CDH13</i>. These data indicate that CDH2 and CDH13 are promising targets for precise treatment of ACC and may serve as new biomarkers for ACC prognosis.