HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer

Anticancer Res. 2018 Nov;38(11):6551-6560. doi: 10.21873/anticanres.13021.

Abstract

Background/aim: The aim of this study was to evaluate the usefulness of biomarkers related to prostate cancer metastasis and survival of patients.

Materials and methods: Proteomics were used for detecting significant differences in protein expression among normal prostate, localized prostate cancer and metastatic cancer using 2-dimensional gel electrophoresis and mass spectrometry. mRNA expression was then examined in order to further confirm significant differences in protein expression. A total of 7 proteins were found to be differentially expressed. Immunochemistry (IHC), was also used to confirm the levels of expression of the 7 proteins in prostate cancer. Survival analysis using the candidate markers was finally performed in 98 metastatic prostate cancer patients according to IHC results.

Results: In metastatic lesions, proteomic analysis indicated that heat shock protein (HSP) 27, prohibitin, glutathione S-transferase 1, fibrinogen β chain, and aldehyde dehydrogenase 6A1 were up-regulated, while α1 antitrypsin, and HSP 60 were down-regulated. IHC revealed that HSP 27, ALDH6A1 and prohibitin were highly specific to metastatic tumor cells. HSP27 and prohibitin appeared more strongly in the incipient stage of cancer than metastatic cancer, and ALDH6A1 was significantly reduced in metastatic cancer (p<0.01). Of all proteins, phohibitin had the highest value in predicting survival. However, all three proteins were a stronger marker than each one separately.

Conclusion: Trio-biomarker composed of HSP27, ALDH6A1 and prohibitin may predict survival of metastatic prostate cancer patients.

Keywords: Prostate cancer; biomarker; metastasis.

MeSH terms

  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Chaperonin 60 / genetics
  • Chaperonin 60 / metabolism
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Gene Expression Regulation, Neoplastic
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism*
  • Humans
  • Male
  • Methylmalonate-Semialdehyde Dehydrogenase (Acylating) / genetics
  • Methylmalonate-Semialdehyde Dehydrogenase (Acylating) / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Neoplasm Metastasis
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Proteomics / methods
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Survival Analysis
  • Up-Regulation*
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin / metabolism

Substances

  • Biomarkers, Tumor
  • Chaperonin 60
  • FGB protein, human
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • HSPD1 protein, human
  • Mitochondrial Proteins
  • Repressor Proteins
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • prohibitin
  • Fibrinogen
  • Aldehyde Oxidoreductases
  • ALDH6A1 protein, human
  • Methylmalonate-Semialdehyde Dehydrogenase (Acylating)