Wu Dong-Hao, Jia Chang-Chang, Chen Jie, Lin Ze-Xiao, Ruan Dan-Yun, Li Xing, Lin Qu, Ma Xiao-Kun, Wan Xiang-Bo, Cheng Na, Chen Zhan-Hong, Xing Yan-Fang, Wu Xiang-Yuan, Wen Jing-Yun
Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Tumour Biol. 2014 Dec;35(12):12225-33. doi: 10.1007/s13277-014-2531-7. Epub 2014 Sep 26.
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.
自噬是一个涉及溶酶体对细胞器进行降解的过程,且与肿瘤的发生和进展密切相关。然而,其在肝细胞癌(HCC)中的重要性仍存在争议。因此,本研究旨在探讨微管相关蛋白1轻链3B(LC3B)和Beclin-1作为自噬标志物在HCC患者中的临床病理作用。采用基于组织芯片的免疫组化方法检测156例可手术切除的HCC患者中LC3B和另一种自噬关键调节因子(Beclin-1)的表达。采用Kaplan-Meier分析、卡方检验和Spearman相关性分析来分析LC3B和Beclin-1的相关性及其对临床特征和预后的影响。我们发现LC3B的表达水平与血管侵犯(P = 0.008)、淋巴结转移(P < 0.001)及Beclin-1表达水平(P < 0.001)显著相关。然而,LC3B与其他临床病理特征无关,包括乙型肝炎病毒感染、肝硬化、肿瘤数量、肿瘤大小、病理分级和肿瘤-淋巴结-转移(TNM)分期。此外,未发现Beclin-1表达与临床病理特征之间存在相关性。生存分析显示,LC3B高表达患者的5年总生存率(OS)低于LC3B低表达患者(高表达组vs.低表达组:79.5% vs. 20.5%,P = 0.026)。并且LC3B高表达倾向于与无进展生存期(PFS)缩短相关(P = 0.074),而Beclin-1的表达水平与OS或PFS无统计学显著相关性。进一步的多因素分析显示,淋巴结转移(P = 0.047)和LC3B表达水平(P = 0.047)是所有患者OS预后的独立预测因素。我们的研究表明,LC3B高表达与血管侵犯和淋巴结转移相关,可能是一种新的预后生物标志物,并且将成为HCC尤其是可手术患者潜在的治疗靶点。