ACAA2 is a Novel Molecular Indicator for Cancers with Neuroendocrine Phenotype

Overview

Journal Br J Cancer

Specialty Oncology

Date 2023 Oct 5

PMID 37798372

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

Affiliations

Soon will be listed here.

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.

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