Int J Med Sci 2015; 12(3):256-263. doi:10.7150/ijms.10735
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
1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
2. Department of Integrative Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
4. NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Liverpool L69 3GA, UK.
5. Department of Molecular and Clinical Cancer Medicine, Institute of Translation medicine, University of Liverpool, Liverpool L69 3GA, UK.
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 HSPA4L, HSPA12A and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA5, HSPA8, HSPA9, HSPAA1, HSPAB1, HSPA14, HSPB11, HSPA13, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPA6, 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), HSPA12A (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 HSPA4 (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), HSPA5 (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and HSPA6 (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 HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.
Keywords: heat shock proteins, carcinoma, hepatocellular, survival, recurrence, BCLC stage, cirrhosis, HSPA12A, HSP90B1, HSPA4, HSPA5, HSPA6, HSP70.
Yang Z, Zhuang L, Szatmary P, Wen L, Sun H, Lu Y, Xu Q, Chen X. 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; 12(3):256-263. doi:10.7150/ijms.10735. Available from http://www.medsci.org/v12p0256.htm