The autophagy marker LC3 strongly predicts immediate mortality after surgical resection for hepatocellular carcinoma

Abstract

The remnant liver's ability to regenerate may affect post-hepatectomy immediate mortality. The promotion of autophagy post-hepatectomy could enhance liver regeneration and reduce mortality. This study aimed to identify predictive factors of immediate mortality after surgical resection for hepatocellular carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their first surgical resection in Taiwan were enrolled between 2010 and 2014. Clinicopathological data and immediate mortality, defined as all cause-mortality within three months after surgery, were analyzed. The expression of autophagy proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by immunohistochemical staining. Approximately 5% of patients had immediate mortality after surgery. The absence of LC3, hypoalbuminemia (<3.5 g/dl), high alanine aminotransferase, and major liver surgery were significantly associated with immediate mortality in univariate analyses. Multivariate logistic regression demonstrated that absence of LC3 (hazard ratio/95% confidence interval: 40.8/5.14-325) and hypoalbuminemia (2.88/1.11-7.52) were significantly associated with immediate mortality. The 3-month cumulative incidence of mortality was 12.1%, 13.0%, 21.4% and 0.4%, respectively, among patients with absence of LC3 expression, hypoalbuminemia, both, or neither of the two. In conclusion, the absence of LC3 expression in adjacent non-tumor tissues and hypoalbuminemia were strongly predictive of immediate mortality after resection for HCC.

Autophagy-dependent apoptosis is triggered by a semi-synthetic [6]-gingerol analogue in triple negative breast cancer cells

“…SSi6 induced, in a concentration-dependent manner, the occurrence of AVOs in MDA-MB-231 cells after 6h of treatment, shown by a strong red fluorescence in the cytoplasm, which was absent in non-malignant MCF-10A cells (Figure 3A ). In addition, an immunostaining assay was performed to detect LC3B, a protein that is considered an autophagy marker [ 12 , 31 ]. Similarly, the induction of autophagy was clear after 6h of SSi6 (50μM) treatment in MDA-MB-231 cells but was absent in non-malignant MCF-10A cells (Figure 3B ).…”

Protection in a model of liver injury is parallel to energy mobilization capacity under distinct nutritional status

“…In parallel and meanwhile, the clinical relevance of autophagy has also emerged in medical fields including surgery and oncology. Recently, the prognostic value of the autophagic marker LC3 was highlighted in two cohorts of patients undergoing liver resection as a surgical cure of hepatocellular carcinoma [24]. In this respect, liver regeneration after extended resections following neoadjuvant therapies represents a main issue where ischemic tolerance and remnant volume are of major interest.…”

Significant predictors of overall survival in patients with hepatocellular carcinoma after surgical resection

“…The relationship between LC3 expression in the non-tumor microenvironment and overall survival has not been discussed in the literature. We have previously reported that a lack of LC3 expression in ANT tissues is associated with immediate death post-hepatectomy [ 35 ]. Here, we show that a lack of LC3 expression in both the tumor and non-tumor liver microenvironments is strongly associated with the poor prognosis of patients with curative hepatectomy for HCC.…”

“…The primary polyclonal antibodies used were anti-LC3 (NB100-2220, Novus Biologicals, Littleton, CO, USA), anti-Beclin-1 (ab51031, Abcam, Cambridge, UK), and anti-p62 (H00008878-M01, Abnova, Taipei, Taiwan). The expression of autophagy-related proteins (LC3, Beclin-1, and p62) was quantitated using the semi-quantitative immunoreactive scoring (IRS) system as described previously [ 35 ], and the expression was defined as either positive (IRS ≥ 2) or negative (IRS <2) based on the products of the intensity and percentage scores. All slides were evaluated independently by two investigators in a blinded manner.…”