High Expression of the Mitophagy-Related Protein Pink1 is Associated with a Poor Response to Chemotherapy and a Poor Prognosis for Patients Treated with Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

Kotaro Yamashita, Hiroshi Miyata, Tomoki Makino, Yasunori Masuike, Haruna Furukawa, Koji Tanaka, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Eiichi Morii, Masaki Mori, Yuichiro Doki

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

Background: 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). Methods: 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. Results: 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. Conclusions: High expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.

本文言語英語
ページ(範囲)4025-4032
ページ数8
ジャーナルAnnals of Surgical Oncology
24
13
DOI
出版ステータス出版済み - 12 1 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

フィンガープリント 「High Expression of the Mitophagy-Related Protein Pink1 is Associated with a Poor Response to Chemotherapy and a Poor Prognosis for Patients Treated with Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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