title: The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling.
abstract: This study reports on the C-terminal fragment of the 11S proteasome activator complex (PA28 or Reg alpha), a novel ovarian-specific biomarker of early and late stages of ovarian cancer (OVC) relapse, in patient biopsies after chemotherapy. A total of 179 tissue samples were analyzed: 8 stage I, 55 stage III-IV, 10 relapsed serous carcinomas, 25 mucinous carcinomas and 12 borderline and 68 benign ovarian tissue samples. This fragment was detected by MALDI mass spectrometry profiling in conjunction with a novel extraction method using hexafluoroisopropanol (1,1,1,3,3,3-hexafluoro-2-propanol; HFIP) solvents for protein solubilization and by immunohistochemistry using a specific antibody directed against the C-terminal fragment of PA28. Due to its specific cellular localization, this fragment is a suitable candidate for early OVC diagnosis, patient prognosis and follow-up during therapy and discriminating borderline cancers. Statistical analyses performed for this marker at different OVC stages reflect a prevalence of 77.66 ± 8.77 % (with a correlation coefficient value p < 0.001 of 0.601 between OVC and benign tissue). This marker presents a prevalence of 88 % in the case of tumor relapse and is detected at 80.5 % in stage I and 81.25 % ± 1.06 in stage III-IV of OVC. The correlation value for the different OVC stages is p < 0.001 of 0.998. Taken together, this report constitutes the first evidence of a novel OVC-specific marker.
authors.affiliation: Laboratoire de Spectrométrie de Masse Biologique Fondamentale et Appliquée, Université Nord de France, EA 4550, Université de Lille 1, Cité Scientifique, 59650 Villeneuve D'Ascq, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Longuespée
authors.forename: Charlotte
authors.initials: C
authors.lastname: Boyon
authors.forename: Céline
authors.initials: C
authors.lastname: Castellier
authors.forename: Amélie
authors.initials: A
authors.lastname: Jacquet
authors.forename: Annie
authors.initials: A
authors.lastname: Desmons
authors.forename: Olivier
authors.initials: O
authors.lastname: Kerdraon
authors.forename: Denis
authors.initials: D
authors.lastname: Vinatier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.forename: Robert
authors.initials: R
authors.lastname: Day
authors.forename: Michel
authors.initials: M
authors.lastname: Salzet
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009124:Muscle Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D009124:Muscle Proteins; C085047:PSME1 protein, human; D046988:Proteasome Endopeptidase Complex