ACAA2 Is a Novel Molecular Indicator for Cancers With Neuroendocrine Phenotype

Authors

Michelle Shen
Shiqin Liu
Angus Toland
En-Chi Hsu
Alifiani B Hartono
Busola R Alabi
Merve Aslan
Holly M Nguyen
Conner J Sessions
Rosalie Nolley
Chanjuan Shi
Jiaoti Huang
James D Brooks
Eva Corey
Tanya Stoyanova

Publication Date

11-1-2023

Journal

British Journal of Cancer

Abstract

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. ACAA2 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.

Keywords

Humans, Male, Carcinoma, Neuroendocrine, Carcinoma, Small Cell, Cell Line, Tumor, Lung Neoplasms, Phenotype, Prostatic Neoplasms, RNA, Messenger, Small Cell Lung Carcinoma

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Supplementary Materials

PMID: 37798372