Chaperone protein l-isoaspartate (d-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma

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• 作者：Heisuke Saito ; MD^a ; Masahiro Yamashita ; MD^a ; ^{yamam@iwate-med.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Masahito Ogasawara ; MD^b ; Noriyuki Yamada^c ; Miyuki Niisato^a ; Makoto Tomoyasu ; MD^d ; Hiroyuki Deguchi ; MD^d ; Tatsuo Tanita ; MD^d ; Kazuyuki Ishida ; MD^c ; Tamotsu Sugai ; MD^c ; Kohei Yamauchi ; MD^a
• 关键词：Lung adenocarcinoma ; Protein-l-isoaspartate (d-aspartyl) O-methyltransferase (PIMT) ; Prognosis ; Disease progression ; Chaperon ; Stage I disease ; Predictor
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：50
• 期：Complete
• 页码：1-10
• 全文大小：1043 K

文摘

Endoplasmic reticulum stress and chaperone dysfunction have recently been associated with poor prognoses in various cancers. The newly discovered chaperone protein l-isoaspartyl (d-aspartyl) O-methyltransferase (PIMT) regulates the viability of cancer cells in various cancers, although no clinical information regarding the relationship between lung cancer and PIMT expression has been reported. In this study, we aimed to elucidate the relationship between PIMT expression and the prognosis of lung adenocarcinoma. Paraffin-embedded lung tissues obtained from 208 patients with surgically resected lung adenocarcinoma were subjected to immunohistochemical analyses using primary antibodies against PIMT. Kaplan-Meier curves, log-rank tests, and the Cox proportional hazards model were used to analyze the association between PIMT expression and patient survival. Strong PIMT expression was detected in 106 (50.9%) patients, being particularly observed in patients with advanced stages of lung adenocarcinoma. Strong PIMT expression was associated with that of 78-kDa glucose-regulated protein, a marker of endoplasmic reticulum stress. Patients with strong PIMT expression had a shorter survival time (Kaplan-Meier analysis, P < .001). Multivariate Cox hazard regression analysis demonstrated that strong PIMT expression was an independent predictor of poor prognosis of lung adenocarcinoma, including those with stage I disease (hazard ratios, 6.45 and 6.81, respectively; 95% confidence intervals, 2.46-16.9 and 1.79-25.8, respectively; P < .001 and P = .005, respectively). Collectively, strong PIMT expression was a predictive marker of poor prognosis for surgically resected lung adenocarcinoma, and this finding might help clinicians determine the need for postoperative adjuvant chemotherapy in patients with stage I lung adenocarcinoma.