ACAA2 is a novel molecular indicator for cancers with neuroendocrine phenotype

Background Neuroendocrine phenotype is commonly associated with therapy resistance and poor prognoses in small-cell neuroendocrine cancers (SCNCs), such as neuroendocrine prostate cancer (NEPC) and small-cell lung cancer (SCLC). Expression levels of current neuroendocrine markers exhibit high case-by-case variability, so multiple markers are used in combination to identify SCNCs. Here, we report that ACAA2 is elevated in SCNCs and is a potential molecular indicator for SCNCs. Methods ACAA2 expressions in tumour xenografts, tissue microarrays (TMAs), and patient tissues from prostate and lung cancers were analysed via immunohistochemistry. ACAA 2 mRNA levels in lung and prostate cancer (PC) patients were assessed in published datasets. Results ACAA2 protein and mRNA levels were elevated in SCNCs relative to non-SCNCs. Medium/high ACAA2 intensity was observed in 78% of NEPC PDXs samples ( N = 27) relative to 33% of adeno-CRPC ( N = 86), 2% of localised PC ( N = 50), and 0% of benign prostate specimens ( N = 101). ACAA2 was also elevated in lung cancer patient tissues with neuroendocrine phenotype. 83% of lung carcinoid tissues ( N = 12) and 90% of SCLC tissues ( N = 10) exhibited medium/high intensity relative to 40% of lung adenocarcinoma ( N = 15). Conclusion ACAA2 expression is elevated in aggressive SCNCs such as NEPC and SCLC, suggesting it is a potential molecular indicator for SCNCs.