title: Apolipoprotein C-II is a potential serum biomarker as a prognostic factor of locally advanced cervical cancer after chemoradiation therapy.
abstract: OBJECTIVE
  To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC).
  
  
  METHODS
  In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak.
  
  
  RESULTS
  The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078).
  
  
  CONCLUSIONS
  ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.
authors.affiliation: Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka, Japan. Electronic address: harima@takii.kmu.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Harima
authors.forename: Koshi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Keita
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Komemushi
authors.forename: Shohei
authors.initials: S
authors.lastname: Kanno
authors.forename: Toshiko
authors.initials: T
authors.lastname: Shiga
authors.forename: Noboru
authors.initials: N
authors.lastname: Tanigawa
mesh_terms: D053304:Apolipoprotein C-II / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001918:Brachytherapy / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016022:Case-Control Studies; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010449:Peptide Mapping / Q000379:methods; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry / Q000379:methods; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D053304:Apolipoprotein C-II; D014408:Biomarkers, Tumor; D007496:Iridium Radioisotopes