Kim Jeong-Won, Jun Sun-Young, Kim Joon-Mee, Oh Young-Ha, Yoon Ghilsuk, Hong Seung-Mo, Chung Joon-Yong
Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Korea.
Department of Pathology, Incheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea.
J Clin Med. 2021 Nov 19;10(22):5398. doi: 10.3390/jcm10225398.
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 (p62), and p62 cytoplasmic (p62) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma ( < 0.001) and high histologic grade ( = 0.029). The combined expression of LC3B and p62 (LC3+/p62+) was related to the older age of patients ( = 0.017), undifferentiated carcinoma ( < 0.001), and high grade ( = 0.031). LC3B+ ( = 0.006), p62+ ( = 0.041), or p62+ ( = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62+ ( = 0.001) or LC3B+/p62+ ( = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor ( = 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.
自噬是一种维持细胞稳态的机制，参与肿瘤细胞在癌症中的生长和存活，并且自噬抑制剂已在抗癌治疗的临床试验中进行了测试。为了阐明自噬在小肠腺癌（SIAC）中的临床和预后意义，我们使用自动定量分析评估了171例手术切除的原发性SIAC中自噬标志物LC3B和p62的表达。分别在23例（13.5%）、52例（30.4%）和43例（25.1%）癌组织中观察到LC3B阳性、p62核阳性（p62核）和p62胞质阳性（p62胞质）表达。LC3B+表达与未分化癌相关（<0.001）和高组织学分级相关（=0.029）。LC3B和p62的联合表达（LC3+/p62+）与患者年龄较大相关（=0.017）、未分化癌相关（<0.001）和高级别相关（=0.031）。LC3B+（=0.006）、p62+（=0.041）或p62+（=0.006）表达与较差的生存率相关。此外，具有LC3B+/p62+（=0.001）或LC3B+/p62+（=0.002）表达的SIAC患者生存时间较短。在多变量分析中，LC3B表达仍然是总生存的独立预后因素（=0.025）。总之，自噬可能在SIAC的肿瘤发生中起作用，并且LC3B和p62可作为SIAC的预后生物标志物和潜在治疗靶点。
