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- Title
Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.
- Authors
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
- Abstract
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.
- Subjects
LIVER cancer; HEAT shock proteins; TRANSCRIPTION factors; GENE expression; MULTIVARIATE analysis; METABOLISM; SURGICAL excision; PROGNOSIS
- Publication
British Journal of Cancer, 2013, Vol 109, Issue 6, p1648
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/bjc.2013.488