Relationship between phosphorylation of sperm-specific antigen and prognosis of lung adenocarcinoma

J Proteomics. 2016 Apr 29:139:60-6. doi: 10.1016/j.jprot.2016.03.005. Epub 2016 Mar 3.

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.

Biological significance: 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.

Keywords: Biomarker; Lung adenocarcinoma; MRM analysis; Phosphorylation; Shotgun LC–MS/MS analysis; Therapeutic target.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / metabolism*
  • Disease-Free Survival
  • Humans
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Membrane Proteins
  • Microfilament Proteins
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Survival Rate

Substances

  • Antigens, Surface
  • ITPRID2 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Neoplasm Proteins