AI Article Synopsis
- Gastric/gastroesophageal junction (GEJ) adenocarcinoma is a complex disease with multiple causes and diverse histological and molecular characteristics, and autophagy processes play a crucial role in its development.
- The study investigated autophagic pathways in gastric adenocarcinoma by analyzing specific proteins (p62, LAMP2A, LC3B) in normal and abnormal gastric tissues.
- Results indicated that dysplastic gastric tissue exhibited distinct autophagic protein expressions, with high nuclear p62 levels correlating to worse survival outcomes, highlighting the variability of autophagy in these cancers.
Article Abstract
Background And Aim: Gastric/gastroesophageal junction (GEJ) adenocarcinoma is a heterogeneous disease, with various etiologies and with tumors encompassing a spectrum of histologic and molecular subtypes. "Autophagy" includes two related but distinct homeostatic processes that promote cell survival under adverse conditions, namely macro- and chaperone-mediated autophagy. There is increasing evidence of the roles autophagy may play in tumorigenesis.
Methods: Autophagic pathways were examined in the context of the heterogeneity intrinsic to gastric/GEJ adenocarcinoma, utilizing immunohistochemistry targeting specific proteins within the pathways (p62, LAMP2A, LC3B). We examined whole sections of normal and dysplastic gastric mucosa, as well as a tissue microarray of adenocarcinomas.
Results: Dysplastic gastric epithelium was marked by frequent nuclear p62 and aberrant LAMP2A expression compared to normal. Examining the pattern of LC3B/cytoplasmic p62 immuno-reactivity in gastric adenocarcinoma demonstrated a predominant pattern of LC3B/p62 staining (56/86, 65.1%), which has been previously associated with active, but impaired macroautophagy. There were no statistically significant associations seen between LC3B/cytoplasmic p62 staining patterns with tumor grade, histotype, or approximated TCGA molecular subtype. LAMP2A and nuclear p62 and staining patterns were also heterogeneous across the cohort, but with no statistically significant associations seen. The prognostic significance of the three proteins was limited, however high nuclear p62 levels were associated with worse overall survival (log-rank -value = 0.0396).
Conclusion: Our data demonstrate the dynamic nature of autophagic proteins in the gastric epithelium, and we expand the biological heterogeneity observed in gastric/GEJ adenocarcinoma to include autophagy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042205 | PMC |
| http://dx.doi.org/10.3389/fonc.2021.555614 | DOI Listing |
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