乙酰辅酶A合成酶2促进肿瘤发生，提示肾细胞癌患者预后不良。

Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma.

作者信息

Zhang Shaojin, He Juanjuan, Jia Zhankui, Yan Zechen, Yang Jinjian

机构信息

Department of Urology Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, China.

Department of Breast Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, China.

出版信息

Urol Oncol. 2018 May;36(5):243.e9-243.e20. doi: 10.1016/j.urolonc.2018.01.013. Epub 2018 Mar 2.

DOI:10.1016/j.urolonc.2018.01.013

PMID:29503142

Abstract

BACKGROUND

Acetyl-CoA synthetase 2 (ACSS2) is highly expressed in various cancers, whereas ACSS2 expression and function in renal cell carcinoma (RCC) are unknown.

METHODS

We investigated ACSS2 expression in 198 human RCC tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. Overexpression and knockdown of ACSS2 were used to investigate the proliferation, migration and invasion of human RCC 786-O, 769-P, and ACHN cell lines.

RESULTS

High-ACSS2 expression was associated with advanced T stage (P = 0.008), advanced tumor-node-metastasis stage (P = 0.015) and high University of California, Los Angeles, Integrated Staging System score category (P = 0.009). Multivariate analysis identified high-ACSS2 expression as a poor prognostic factor for recurrence-free survival (hazard ratio [HR] = 1.83, P = 0.038) and overall survival (HR = 1.60, P = 0.043). Cell-based functional assays showed that ACSS2 knockdown inhibited RCC cell growth, migration, and invasion, whereas overexpression of ACSS2 enhanced these effects. ACSS2 silencing inhibited PI3K/AKT signaling pathway.

CONCLUSION

ACSS2 may increase tumor progression and aggressive behavior and be an independent prognostic factor in RCC.

摘要

背景

乙酰辅酶A合成酶2（ACSS2）在多种癌症中高表达，而其在肾细胞癌（RCC）中的表达及功能尚不清楚。

方法

我们采用免疫组化法研究了198例人类RCC组织中ACSS2的表达，并分析了其与临床病理的相关性及预后意义。通过ACSS2的过表达和敲低来研究其对人RCC 786 - O、769 - P和ACHN细胞系增殖、迁移和侵袭的影响。

结果

ACSS2高表达与晚期T分期（P = 0.008）、晚期肿瘤-淋巴结-转移分期（P = 0.015）及高加利福尼亚大学洛杉矶分校综合分期系统评分类别（P = 0.009）相关。多因素分析确定ACSS2高表达是无复发生存期（风险比[HR] = 1.83，P = 0.038）和总生存期（HR = 1.60，P = 0.043）的不良预后因素。基于细胞的功能分析表明，ACSS2敲低抑制RCC细胞的生长、迁移和侵袭，而ACSS2过表达则增强这些作用。ACSS2沉默抑制PI3K/AKT信号通路。