title: The autophagy-related marker LC3 can predict prognosis in human hepatocellular carcinoma.
abstract: BACKGROUND
  Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.
  
  
  METHODS
  The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis.
  
  
  RESULTS
  LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.
  
  
  CONCLUSIONS
  Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Hah
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Ha
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Kang
authors.forename: Koo Jeong
authors.initials: KJ
authors.lastname: Kang
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Hwang
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Chung
authors.forename: Kwang Bum
authors.initials: KB
authors.lastname: Cho
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Park
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Seo
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: Byoung Kuk
authors.initials: BK
authors.lastname: Jang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D051742:Transcription Factor CHOP