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前列腺癌中致癌性ACSM1是通过代谢和细胞外基质-受体相互作用信号通路发挥作用的。

Oncogenic ACSM1 in prostate cancer is through metabolic and extracellular matrix-receptor interaction signaling pathways.

作者信息

Guo Yongchen, Ren Chunna, Huang Wentao, Yang Wancai, Bao Yonghua

机构信息

Department of Immunology, Mudanjiang Medical University Mudanjiang 157011, China.

The Second Affiliated Hospital of Mudanjiang Medical University Mudanjiang 157011, China.

出版信息

Am J Cancer Res. 2022 Apr 15;12(4):1824-1842. eCollection 2022.

Abstract

Acyl-coenzyme A synthetase medium chain family member 1 (ACSM1) is a medium chain Acyl-CoA Synthetase family member and plays an important role in fatty acid metabolism. The oncogenic roles of ACSM1 are largely unknown. Using comprehensive approaches, we analyzed gene expression profiles and genomic datasets and identified that the expression of ACSM1 was specifically increased in prostate cancer in comparison to the adjacent non-tumor tissues. The increased expression of ACSM1 was associated with increased risks of poor prognosis and shorter survival time. Moreover, genomic copy number alterations of ACSM1, including deletion, amplification, and amino acid changes were frequently observed in prostate cancers, although these mutations did not correlate with gene expression levels. However, ACSM1 gene amplifications were significantly corrected with increased risks of prostate cancer metastasis, and ACSM1 genetic alterations were significantly associated with worse disease-free. And progress-free survival. Gene function stratification and gene set enrichment analysis revealed that the oncogenic roles of ACSM1 in prostate cancer were mainly through metabolic pathways and extracellular matrix (ECM)-receptor interaction signaling pathways, but not associated with microenvironmental immunological signaling pathways, and that ACSM1 expression was not associated with immune cell infiltration in the cancer microenvironment or prostate cancer immune subtypes. In conclusion, the present work has demonstrated that ACSM1 can be specifically and significantly elevated in prostate cancer. ACSM1 gene expression and genomic amplification exhibit important clinical significance through metabolic and ECM-receptor interaction signaling pathways. Thus, ACSM1 may be a novel oncogene and serve as a biomarker for prostate cancer screening and prognosis prediction, and/or a therapeutic target.

摘要

酰基辅酶A合成酶中链家族成员1(ACSM1)是中链酰基辅酶A合成酶家族成员,在脂肪酸代谢中起重要作用。ACSM1的致癌作用在很大程度上尚不清楚。我们采用综合方法分析了基因表达谱和基因组数据集,发现与相邻的非肿瘤组织相比,ACSM1在前列腺癌中的表达特异性增加。ACSM1表达增加与预后不良风险增加和生存时间缩短有关。此外,虽然这些突变与基因表达水平无关,但在前列腺癌中经常观察到ACSM1的基因组拷贝数改变,包括缺失、扩增和氨基酸变化。然而,ACSM1基因扩增与前列腺癌转移风险增加显著相关,ACSM1基因改变与无病生存期和无进展生存期较差显著相关。基因功能分层和基因集富集分析表明,ACSM1在前列腺癌中的致癌作用主要通过代谢途径和细胞外基质(ECM)-受体相互作用信号通路,但与微环境免疫信号通路无关,且ACSM1表达与癌症微环境中的免疫细胞浸润或前列腺癌免疫亚型无关。总之,目前的研究表明ACSM1在前列腺癌中可特异性且显著升高。ACSM1基因表达和基因组扩增通过代谢和ECM-受体相互作用信号通路具有重要的临床意义。因此,ACSM1可能是一种新型癌基因,可作为前列腺癌筛查和预后预测的生物标志物,和/或治疗靶点。

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