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.

Specific c-Jun target genes in malignant melanoma

“…37,38 In contrast to our melanoma data, Wu and colleagues described MAP1LC3B overexpression in hepatocellular carcinoma and its correlation with malignant progression and poor prognosis. 39 Interestingly, our study showed down-regulation of MAP1LC3B in melanoma cells, which was previously and concordantly with our findings observed in hypopharyngeal squamous cell carcinoma (HSCC) correlating with poor prognosis. 40 Therefore, we speculate that the status and role of MAP1LC3 expression vary across cancer types.…”

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis

“…LC3, the mammalian homolog of the yeast Atg8p, is considered as the crucial component of autophagosomes (Maruyama et al 2014). It includes three isoforms of LC3A, LC3B, LC3C, of which LC3B is associated with autophagy levels (Wu et al 2014a). LC3 has been reported in several tumors (including ovarian cancer (Shen et al 2008), brain cancer (Ghavami et al 2014), colorectal cancer (Wu et al 2015), prostate cancer (Zhang et al 2017), breast cancer (Jiang et al 2017), melanoma (Segala et al 2017).…”

Axl and autophagy LC3 expression in tumors is strongly associated with clinical prognosis of hepatocellular carcinoma patients after curative resection

“…Previous studies of LC3 expression in terms of clinical outcomes have reported controversial results. [21][22][23] Our previous work showed that high LC3 levels in both the liver and tumor microenvironments are significantly correlated with decreased HCC recurrence and increased OS after surgical resection. High LC3 expression seems to have a protective effect on clinical outcomes, including HCC recurrence and OS after hepatectomy.…”