title: 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.
abstract: 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.
authors: 1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
authors: Zongguo
authors: Z
authors: Yang
authors: 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.
authors: Liping
authors: L
authors: Zhuang
authors: 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.
authors: Peter
authors: P
authors: Szatmary
authors: 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.
authors: Li
authors: L
authors: Wen
authors: 1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
authors: Hua
authors: H
authors: Sun
authors: 1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
authors: Yunfei
authors: Y
authors: Lu
authors: 1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
authors: Qingnian
authors: Q
authors: Xu
authors: 1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
authors: Xiaorong
authors: X
authors: Chen
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050957:HSP110 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C472130:HSPA12A protein, human; C121993:HSPA4 protein, human; C000717247:HSPA5 protein, human; C544598:HSPA6 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin
keywords: BCLC stage; HSP70.; HSP90B1; HSPA12A; HSPA4; HSPA5; HSPA6; carcinoma, hepatocellular; cirrhosis; heat shock proteins; recurrence; survival