title: Relationship between phosphorylation of sperm-specific antigen and prognosis of lung adenocarcinoma.
abstract: Lung cancer is generally considered as a highly malignant cancer. A major challenge for the management of lung adenocarcinoma patients is to predict the clinical course of the disease after resection. We analyzed the different levels of phosphorylation of proteins in lung adenocarcinoma tissues between a poor prognosis (PP) group, in which six patients exhibited recurrence within five years after surgery, and a good prognosis (GP) group, in which seven patients did not exhibit recurrence within five years after surgery. We found that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2) [phospho-SSFA2(pS92)] was stimulated in the PP group. Using samples from a total of 46 patients, we investigated the utility of phospho-SSFA2(pS92) to discriminate patients of GP and PP groups, with multiple reaction monitoring (MRM) mass spectrometry. Consequently, we confirmed that the PP group had significantly elevated phospho-SSFA2(pS92) levels. Additionally, no expression of SSFA2 recognized in the normal lung tissues. From these results, we demonstrate that phospho-SSFA2 (pS92) is related to the prognosis of early resected lung adenocarcinomas. Therefore, we suggest that phosphorylation of this protein indicates its role as a potential biomarker and new therapeutic target.
  
  
  CONCLUSIONS
  Lung adenocarcinoma patients often experience a high rate of recurrence after surgery. It is important to discover biomarkers for prognostic prediction and therapeutic targets for treatment of early-stage lung adenocarcinoma. In this study, using tissue samples obtained from patients with lung adenocarcinoma that had been stored for five years at -80°C, we identified 13 unique phosphorylated peptides, which were differentially expressed between poor and good prognosis groups. We confirmed that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2)[phospho-SSFA2 (pS92)], was related to poor prognosis. Our study demonstrates that prognostic prediction of early-stage lung adenocarcinoma is possible, and suggests new therapeutic targets for its treatment.
authors.affiliation: Yokohama City University, Graduate School of Medical Life Science and Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Okayama
authors.affiliation: Yokohama City University, Graduate School of Medical Life Science and Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Oshita
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Thoracic Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Microbiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Electronic address: aryo@yokohama-cu.ac.jp.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.affiliation: Yokohama City University, Graduate School of Medical Life Science and Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Electronic address: hirano@yokohama-cu.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D015996:Survival Rate
chemical_list: D000954:Antigens, Surface; C482653:ITPRID2 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins
keywords: Biomarker; Lung adenocarcinoma; MRM analysis; Phosphorylation; Shotgun LC–MS/MS analysis; Therapeutic target