title: Chaperone protein L-isoaspartate (D-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Heisuke
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan. Electronic address: yamam@iwate-med.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Pharmacology, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogasawara
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Niisato
authors.affiliation: Department of Pulmonary Surgery, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomoyasu
authors.affiliation: Department of Pulmonary Surgery, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Deguchi
authors.affiliation: Department of Pulmonary Surgery, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Tanita
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Morioka, 020-8505, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamauchi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C435725:PCMT1 protein, human; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase
keywords: Chaperon; Disease progression; Lung adenocarcinoma; Predictor; Prognosis; Protein-l-isoaspartate (d-aspartyl) O-methyltransferase (PIMT); Stage I disease