The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling

Histochem Cell Biol. 2012 Jul;138(1):141-54. doi: 10.1007/s00418-012-0953-0. Epub 2012 Apr 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Early Diagnosis
  • Female
  • Humans
  • Immunohistochemistry
  • Muscle Proteins / analysis*
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proteasome Endopeptidase Complex / analysis*
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers, Tumor
  • Muscle Proteins
  • PSME1 protein, human
  • Proteasome Endopeptidase Complex