title: Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma.
abstract: Autophagy is a process that involves lysosomal degradations of cellular organelles and closely related to tumor occurrence and progression. However, its importance in hepatocellular carcinoma (HCC) was still controversial. Therefore, this study is aimed to address the clinicopathologic effect of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin-1, as autophagic markers, in HCC patients. Tissue microarray-based immunohistochemistry was used to examine the expression of LC3B and another autophagy key regulator (Beclin-1) in 156 operable HCC patients. Kaplan-Meier analysis, chi-square test, and Spearman's correlation analysis were used to analyze correlation of LC3B and Beclin-1 and their influence on clinical characteristics and prognosis. We found that the expression level of LC3B was significantly associated with vascular invasion (P = 0.008), lymph node metastasis (P < 0.001), and Beclin-1 expression level (P < 0.001). However, LC3B was not related to other clinicopathological features, including hepatitis B virus infection, liver cirrhosis, tumor number, tumor size, pathology grade, and tumor-node-metastasis (TNM) stage. Besides, correlation between the expression of Beclin-1 and clinicopathological features were not identified. Survival analysis showed that patients with high LC3B expression had a poorer 5-year overall survival (OS) rate than those with low LC3B expression (high vs. low: 79.5 % vs. 20.5 %, P = 0.026). And high LC3B expression tended to be related with shorter progression-free survival (PFS) (P = 0.074), whereas the expression level of Beclin-1 did not show statistically significant association with OS or PFS. Further multivariate analysis revealed that lymph node metastasis (P = 0.047) and LC3B expression level (P = 0.047) were independent factors to predict the prognosis of OS in all patients. Our study demonstrated that high expression of LC3B, correlated with vascular invasion and lymph node metastasis, might be a novel prognostic biomarker and would be a potential therapy target for HCC, especially in operable patients.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Dong-Hao
authors.initials: DH
authors.lastname: Wu
authors.forename: Chang-Chang
authors.initials: CC
authors.lastname: Jia
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Ze-Xiao
authors.initials: ZX
authors.lastname: Lin
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Ruan
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.lastname: Min-Dong
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Ma
authors.forename: Xiang-Bo
authors.initials: XB
authors.lastname: Wan
authors.forename: Na
authors.initials: N
authors.lastname: Cheng
authors.forename: Zhan-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xing
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins