Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas

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.

Basal level of autophagy and MAP1LC3B‐II as potential biomarkers for DHA‐induced cytotoxicity in colorectal cancer cells

“…Adams et al . explored the prognostic relevance of MAP1LC3B and SQSTM1 in esophageal adenocarcinomas (EAC) and demonstrated that low MAP1LC3B and SQSTM1 protein levels correlated with worse outcome and more aggressive tumors in a cohort of patients with EAC. In line with this, patients with tumors with low MAP1LC3B‐II levels could potentially benefit from an alternative treatment strategy with omega‐3 fatty acids in combination with conventional cancer treatment.…”

p62/SQSTM1—Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer

“…p62 is ubiquitously expressed in various cell types , mainly in the cytoplasm, and is also present in the nucleus, autophagosomes, and lysosomes . p62 is overexpressed in many types of human cancer, including hepatocellular carcinoma (HCC) , intrahepatic cholangiocarcinoma , pancreatic cancer , lung cancer , oral, head and neck cancer , esophageal cancer , gastric cancer , colon cancer , breast cancer , prostate cancer , melanoma , endometrial cancer , ovarian cancer , and kidney cancer , as well as chronic liver diseases, such as alcoholic and nonalcoholic steatohepatitis (ASH, NASH) that increase HCC risk . Therefore, a p62‐encoding DNA plasmid vaccine may be useful for cancer immunotherapy .…”

p62/SQSTM1 expression in canine mammary tumours: Evolutionary notes

“…Numerous studies report different p62 expression patterns in different types of human cancers of different origins: the protein is overexpressed in prostate, digestive system, liver and lung carcinoma or down‐regulated in oesophageal adenocarcinomas and colorectal cancers …”

“…In thyroid carcinomas, p62 expression changes according to the different histologic sub‐types, with higher expression in the papillary type compared to the follicular type . In cutaneous stage II melanomas p62 is considered as prognostic marker, moreover oesophageal adenocarcinomas with low total p62 expression (nuclear and cytoplasmic) have a worse prognosis . In human colorectal tumours however, cytoplasmic p62 immunostaining has been correlated with a favourable prognosis .…”