Correlations of sympathetic nerve pathway gene expression signatures with survival for salivary ACC and myoepithelial carcinoma. (A) Kaplan–Meier survival curves using sympathetic nerve gene expression signature IPAS scores. High- and low-expression groups are stratified by lowest P value. Log-rank (Mantel–Cox) test (n = 54). (B) Heatmap of IPAS scores generated for neuronal pathway gene expression signatures for primary salivary ACC (sorted based on TNM stage), metastatic ACC, and primary myoepithelial carcinoma. (C) IPAS score heatmap generated for neuronal pathway gene expression signatures for two ACC patients with synchronous primary and metastatic lesions. (D) Quantification of large-caliber TH⁺ nerve density in primary salivary ACC (n = 12) and in lung metastases (n = 6) (Student’s t test, *P < 0.05). (E) Left: Single-cell RNA-seq data of ACC cells. UMAPs of primary malignant ACC cells showing the expression level of gene signatures scores for NE secretion, NE transport, and β2R downstream pathway. Right: Boxplot of pathway scores of each primary ACC cell (horizontal lines denote median values, and boxes extend from the first and third quartiles; vertical extending lines denote adjacent values). (F) A scatterplot of single-cell RNA-seq data of ACC cells shows a significant, positive correlation between NE transport and β2R downstream pathway gene expression in seven patients (Pearson’s correlation, R = 0.84, P = 0.017).