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Upregulation of heat shock proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in tumour tissues is associated with poor outcomes from HBV-related early-stage hepatocellular carcinoma.

Int J Med Sci. 2015 Feb 15;12(3):256-63. eCollection 2015
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摘要


BACKGROUND:Heat shock proteins (HSPs) are overexpressed in human hepatocellular carcinoma (HCC) tissue and correlate with aggressiveness and prognosis of HCC. METHODS:Using the GSE14520 microarray expression profile from Gene Expression Omnibus, we compared HSP gene expression between tumour and non-tumour tissues and correlated this with outcomes in HCC patients. RESULTS:We analysed 220 hepatitis B virus (HBV)-related HCC patients and 25 HSPs in this study. With the exception of and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPB11, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPB2 and HSPB3 were upregulated in non-tumour tissues (all P < 0.001). Multivariate analysis showed that cirrhosis (HR = 5.282, 95% CI = 1.294-21.555, P = 0.02), Barcelona Clinic liver cancer (BCLC) staging (HR = 2.151, 95% CI = 1.682-2.750, P < 0.001), Hduanyu184212A (HR = 1.042, 95% CI = 1.003-1.082, P = 0.033) and HSP90B1 (HR = 1.001, 95% CI = 1.000-1.001, P = 0.011) were negatively associated with survival of HBV-related HCC patients. Furthermore, advanced BCLC staging (HR = 1.797, 95% CI = 1.439-2.244, P < 0.001) was also associated with earlier recurrence of HCC. The high expression of (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and (HR = 1.008, 95% CI = 1.001-1.015, P = 0.021) was similarly associated with HCC recurrence. CONCLUSIONS:The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of Hduanyu184212A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of Hduanyu18424, Hduanyu18425 and Hduanyu18426 might be associated with earlier recurrence of HCC.

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