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Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas. | LitMetric

AI Article Synopsis

  • Esophageal adenocarcinomas (EAC) are aggressive tumors that often resist chemotherapy, and the study investigates the role of basal autophagy in these cancers.
  • An increase in proteins LC3B and p62, related to autophagy, was observed in EAC cell lines treated with an autophagy inhibitor, indicating active basal autophagy.
  • The study found that high expression levels of LC3B and p62 correlated with earlier tumor stages and better prognosis, while low levels of these proteins were linked to more aggressive tumor behavior, suggesting a need for targeted therapies that regulate autophagy.

Article Abstract

Esophageal adenocarcinomas (EAC) are aggressive tumors with considerable rates of chemoresistance. Autophagy is a lysosome-dependent degradation process, characterized by the formation of vesicles called autophagosomes, and has been implicated in cancer. Protein light chain 3 B (LC3B) and p62 are associated with autophagosomal membranes and degraded. We aimed to assess the impact of basal autophagy on EAC. In EAC cell lines, an increase in LC3B and p62 was observed with increasing concentrations of the autophagy inhibitor chloroquine, which indicates functional basal autophagy. LC3B and p62 immunohistochemistry was performed on primary resected EAC. High LC3B and p62 expression was associated with earlier tumor stages (p < 0.05). High nuclear and cytoplasmic p62 staining were associated with a better prognosis (p = 0.006; p = 0.028). Various combinations of p62 expression with or without LC3B expression identified different prognostic groups. Tumors with low total p62 (p = 0.007) or low LC3B/low p62 expression had the worst outcome (p = 0.007; p = 0.005). A combination score of dot-like/cytoplasmic p62 and nuclear p62 staining was an independent prognostic parameter (p = 0.033; HR = 0.6). This study highlights the potential significance of basal autophagy in EAC biology. Tumors with low LC3B and p62 expression show the most aggressive behavior and may be candidates for autophagy regulating therapeutics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129929PMC
http://dx.doi.org/10.18632/oncotarget.9649DOI Listing

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