Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China.
Pharmacol Res. 2023 Aug;194:106822. doi: 10.1016/j.phrs.2023.106822. Epub 2023 Jun 17.
Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate is less than 10%, even in developed countries such as the USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur in PC. Macroautophagy/autophagy is a cell death process that is maintained at a basal level in physiological conditions, whereas its level often changes during tumorigenesis. The function of autophagy in human cancers is dual and can be oncogenic and onco-suppressor. Autophagy is a potent controller of tumorigenesis in PC. The supportive autophagy in PC escalates the growth rate of PC cells and its suppression can mediate cell death. Autophagy also determines the metastasis of PC cells, and it can control the EMT in affecting migration. Moreover, starvation and hypoxia can stimulate glycolysis, and glycolysis induction can be mediated by autophagy in enhancing tumorigenesis in PC. Furthermore, protective autophagy stimulates drug resistance and gemcitabine resistance in PC cells, and its inhibition can enhance radiosensitivity. Autophagy can degrade MHC-I to mediate immune evasion and also regulates polarization of macrophages in the tumor microenvironment. Modulation of autophagy activity is provided by silibinin, ursolic acid, chrysin and huaier in the treatment of PC. Non-coding RNAs are also controllers of autophagy in PC and its inhibition can improve therapy response in patients. Moreover, mitophagy shows dysregulation in PC, which can enhance the proliferation of PC cells. Therefore, a bioinformatics analysis demonstrates the dysregulation of autophagy-related proteins and genes in PC as biomarkers.
胰腺癌（PC）是一种严重的消化道疾病，即使在美国等发达国家，其 5 年生存率也低于 10%。PC 中经常发生基因组特征改变和失调的生物学机制。自噬是一种细胞死亡过程，在生理条件下维持在基础水平，而在肿瘤发生过程中其水平经常发生变化。自噬在人类癌症中的功能是双重的，可以是致癌的，也可以是抑癌的。自噬是 PC 肿瘤发生的有力控制器。PC 中的支持性自噬会加速 PC 细胞的生长速度，而其抑制作用则可以介导细胞死亡。自噬还决定了 PC 细胞的转移能力，并通过影响迁移来控制 EMT。此外，饥饿和缺氧会刺激糖酵解，而自噬可以通过诱导糖酵解来增强 PC 中的肿瘤发生。此外，保护性自噬会刺激 PC 细胞的耐药性和吉西他滨耐药性，而其抑制作用可以增强放射敏感性。自噬可以降解 MHC-I 来介导免疫逃避，并调节肿瘤微环境中巨噬细胞的极化。水飞蓟素、熊果酸、白杨素和槐耳在治疗 PC 中通过调节自噬活性提供了治疗作用。非编码 RNA 也是 PC 中自噬的控制器，其抑制作用可以改善患者的治疗反应。此外，PC 中的线粒体自噬失调，可增强 PC 细胞的增殖。因此，生物信息学分析表明，自噬相关蛋白和基因在 PC 中的失调可作为生物标志物。
