Abstract
Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.
Highlights
Small bowel cancer is rare in Korea, with 976 new cases occurring in 2018 [1]
Out of the enrolled pN0 197 primary Small intestinal adenocarcinoma (SIAC), 171 (86.8%) with 77 interpretable immuno46.4 histochemical and molecular results were analyzed in this study (Table 1)
The present study highlights the prognostic impact of autophagy-related markers, light chain 3 B (LC3B) and p62, in SIACs
Summary
Small bowel cancer is rare in Korea, with 976 new cases occurring in 2018 [1]. its incidence is increasing; it reached 1.9 per 100,000 in 2018 compared to 0.9 per100,000 in 2003 [2]. The mucosal surface of the small bowel covers >90% of the digestive canal, the overall prevalence of SIAC among carcinomas of the tubular GI tract is
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