ACAA2 是一种新型的具有神经内分泌表型的癌症分子标志物。

ACAA2 is a novel molecular indicator for cancers with neuroendocrine phenotype.

机构信息

Department of Radiology, Stanford University, Stanford, CA, USA.

Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, USA.

出版信息

Br J Cancer. 2023 Nov;129(11):1818-1828. doi: 10.1038/s41416-023-02448-y. Epub 2023 Oct 5.

DOI:10.1038/s41416-023-02448-y

PMID:37798372

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10667239/

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.

摘要

背景

神经内分泌表型通常与小细胞神经内分泌癌（SCNC）的治疗耐药和预后不良相关，如神经内分泌前列腺癌（NEPC）和小细胞肺癌（SCLC）。目前神经内分泌标志物的表达水平存在很高的个体间变异性，因此通常会结合使用多种标志物来识别 SCNC。在此，我们报告 ACAA2 在 SCNC 中上调，并且是 SCNC 的潜在分子标志物。

方法

通过免疫组织化学分析肿瘤异种移植物、组织微阵列（TMA）和来自前列腺癌和肺癌患者的组织中 ACAA2 的表达。在已发表的数据集评估了肺癌和前列腺癌（PC）患者的 ACAA2 mRNA 水平。

结果

与非 SCNC 相比，SCNC 中的 ACAA2 蛋白和 mRNA 水平升高。在 27 例 NEPC PDXs 样本中观察到中等/高强度 ACAA2 （N=27），而在 86 例 adeno-CRPC（N=86）、50 例局部 PC（N=50）和 101 例良性前列腺标本（N=101）中观察到 33%。在具有神经内分泌表型的肺癌患者组织中也观察到 ACAA2 上调。在 12 例肺类癌组织（N=12）和 10 例 SCLC 组织（N=10）中观察到中等/高强度，而在 15 例肺腺癌组织（N=15）中观察到 40%。