Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.
Ann Surg Oncol. 2017 Dec;24(13):4025-4032. doi: 10.1245/s10434-017-6096-8. Epub 2017 Oct 11.
Autophagy plays a major role in cellular homeostasis and is implicated in cancer progression. Damaged mitochondria are scavenged and eliminated by mitochondrial autophagy, referred to as mitophagy, which can promote cancer cell survival. This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in human esophageal squamous cell carcinoma (ESCC).
Both LC3 and Pink1 were analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159 patients undergoing neoadjuvant chemotherapy. The relationships between LC3 and Pink1 expression and various clinicopathologic factors were determined. In vitro assays were performed to assess the role of LC3 and Pink1 in ESCC chemoresistance.
High LC3 expression was observed in 47.9% and high Pink1 expression in 48.4% of the ESCC patients. Pink1 expression was significantly higher in patients who underwent chemotherapy than in patients who did not (p = 0.032). High LC3 and Pink1 expression was significantly correlated with poor response to chemotherapy (p = 0.004 and p < 0.001, respectively), and high expression of Pink1, but not LC3, was significantly correlated with a poor prognosis for patients treated with preoperative chemotherapy (p = 0.007). Multivariate analysis identified Pink1 expression as an independent prognostic factor (p = 0.042). In vitro assays demonstrated that LC3-II and Pink1 expression increased after chemotherapeutic treatment in the ESCC cell line, and inhibition of autophagy and mitophagy using chloroquine and siPink1, respectively, restored chemosensitivity.
High expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.
自噬在细胞内稳态中起着重要作用，并与癌症进展有关。受损的线粒体被称为线粒体自噬（mitophagy）的吞噬和消除，这可以促进癌细胞的存活。本研究调查了自噬相关蛋白 LC3 和线粒体自噬相关蛋白 Pink1 在人食管鳞状细胞癌（ESCC）中的表达和作用。
在 217 名 ESCC 患者的组织中，通过免疫组织化学分析了 LC3 和 Pink1，其中包括 159 名接受新辅助化疗的患者。确定了 LC3 和 Pink1 表达与各种临床病理因素之间的关系。进行了体外试验以评估 LC3 和 Pink1 在 ESCC 化疗耐药性中的作用。
在 47.9%的 ESCC 患者中观察到高 LC3 表达，在 48.4%的患者中观察到高 Pink1 表达。接受化疗的患者的 Pink1 表达明显高于未接受化疗的患者（p=0.032）。高 LC3 和 Pink1 表达与对化疗反应差显著相关（p=0.004 和 p<0.001），而高 Pink1 表达（而不是 LC3）与接受术前化疗的患者预后不良显著相关（p=0.007）。多变量分析确定 Pink1 表达是独立的预后因素（p=0.042）。体外试验表明，在 ESCC 细胞系中，化疗后 LC3-II 和 Pink1 表达增加，用氯喹抑制自噬和用 siPink1 抑制线粒体自噬分别恢复了化疗敏感性。
高 Pink1 表达与 ESCC 患者接受新辅助化疗的化疗耐药性和预后不良相关。
