Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.
Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.
复制标题
瘤周热休克因子1对肝细胞癌切除患者的预后价值
DOI：
10.1038/bjc.2013.488
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发表时间：
2013-09-17
影响因子：
8.8
通讯作者：
Fan, J.
中科院分区：
文献类型：
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作者：
Zhang, J-B;Guo, K.;Sun, H-C;Zhu, X-D;Zhang, B.;Lin, Z-H;Zhang, B-H;Liu, Y-K;Ren, Z-G;Fan, J.
关键词：
背景：肝细胞癌细胞与瘤周微环境中异常代谢信号的相互作用改变了我们对肝癌发生的认识。热休克转录因子-1(HSF1)作为一种不可或缺的应激调节因子，在肝细胞癌微环境中的临床意义尚未明确。方法：对332例肝细胞癌和配对的癌旁肝组织中HSF1的表达进行半定量分析，并与临床病理参数(患者预后)进行相关性分析。结果：HSF1在瘤周组织中高表达，而在肝细胞癌组织中不表达，与总生存期(OS)和复发时间(TTR)，尤其是早期复发(ER)相关，验证队列进一步证实了这一点。多因素分析显示，HSF1的预后与其他临床病理因素无关(OS风险比=2.6，P=0.002；TTR值=2.52，P=0.001)。值得注意的是，HSF1在L02中的下调显著降低了MCT4的表达。L02-shRNA-HSF1在低氧而不是常氧条件下的培养上清液抑制了肝癌细胞的定植和增殖。结论：HSF1高表达可作为高危肝细胞癌ER的敏感读数，可作为根治性切除后潜在的代谢干预靶点。
Background:The cross-talk of hepatocellular carcinoma (HCC) cells and abnormal metabolic signals in peritumoral microenvironment modifies our knowledge of hepatocarcinogenesis. As an indispensable modulator of various stresses, the clinical significance of heat-shock transcription factor-1 (HSF1) in HCC microenvironment has never been defined.Methods:Hepatocellular carcinoma and matched peritumoral liver tissues (n= 332) were semiquantitatively analysed for HSF1 expression, followed by correlation with clinicopathological parameters (patient outcomes). Moreover, the effects of HSF1 deficiency in L02 on monocarboxylate transporter-4 (MCT4) and HCC cells’ colonisation and proliferation were investigated.Results:High expression of HSF1 in peritumoral tissue but not in HCC tissue was associated with poorer overall survival (OS) and time to recurrence (TTR), especially early recurrence (ER), which was further reconfirmed in validation cohort. Multivariate analysis showed that prognostic performance of peritumoral HSF1 was independent of other clinicopathological factors (hazard ratio for OS= 2.60, P= 0.002, for TTR= 2.52, P< 0.001). Notably, downregulation of HSF1 in L02 decreased MCT4 expression significantly. The supernatant from L02-shRNA-HSF1 in hypoxia, NOT normoxia condition, inhibited HCC cell colonisation and proliferation. Moreover, the combination of peritumoral HSF1 and MCT4 was the best predictor for ER and OS.Conclusion:High peritumoral HSF1 expression can serve as a sensitive ‘readout’for high-risk HCC ER, and could be a potential metabolic intervention target following curative resection.
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DOI：
10.1007/978-3-642-03503-6_8
发表时间：
2011-01-01
期刊：
INFLAMMATION AND GASTROINTESTINAL CANCERS
影响因子：
--
作者：
Alison, Malcolm R.;Nicholson, Linda J.;Lin, Wey-Ran
通讯作者：
Lin, Wey-Ran
影响因子：
3.4
作者：
Feng, JT;Liu, YK;Tang, ZY
通讯作者：
Tang, ZY
影响因子：
64.5
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
3.4
作者：
Luk, JM;Lam, CT;Fan, ST
通讯作者：
Fan, ST
DOI：
10.1158/1078-0432.ccr-11-1000
发表时间：
2012-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Neckers L;Workman P
通讯作者：
Workman P