Improving the Prediction of Prostate Cancer Overall Survival by Supplementing Readily Available Clinical Data with Gene Expression Levels of IGFBP3 and F3 in Formalin-Fixed Paraffin Embedded Core Needle Biopsy Material

PLoS One. 2016 Jan 5;11(1):e0145545. doi: 10.1371/journal.pone.0145545. eCollection 2016.

Abstract

Background: A previously reported expression signature of three genes (IGFBP3, F3 and VGLL3) was shown to have potential prognostic value in estimating overall and cancer-specific survivals at diagnosis of prostate cancer in a pilot cohort study using freshly frozen Fine Needle Aspiration (FNA) samples.

Methods: We carried out a new cohort study with 241 prostate cancer patients diagnosed from 2004-2007 with a follow-up exceeding 6 years in order to verify the prognostic value of gene expression signature in formalin fixed paraffin embedded (FFPE) prostate core needle biopsy tissue samples. The cohort consisted of four patient groups with different survival times and death causes. A four multiplex one-step RT-qPCR test kit, designed and optimized for measuring the expression signature in FFPE core needle biopsy samples, was used. In archive FFPE biopsy samples the expression differences of two genes (IGFBP3 and F3) were measured. The survival time predictions using the current clinical parameters only, such as age at diagnosis, Gleason score, PSA value and tumor stage, and clinical parameters supplemented with the expression levels of IGFBP3 and F3, were compared.

Results: When combined with currently used clinical parameters, the gene expression levels of IGFBP3 and F3 are improving the prediction of survival time as compared to using clinical parameters alone.

Conclusion: The assessment of IGFBP3 and F3 gene expression levels in FFPE prostate cancer tissue would provide an improved survival prediction for prostate cancer patients at the time of diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy, Large-Core Needle
  • Cohort Studies
  • Formaldehyde / chemistry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Paraffin Embedding / methods
  • Prognosis
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Thromboplastin / genetics*
  • Tissue Fixation / methods

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Formaldehyde
  • Thromboplastin

Grant support

This work was financed by Uppsala Bio (http://www.uppsalabio.com/), the Swedish Cancer Society (http://www.cancerfonden.se/sv/Information-in-English/), the King Gustaf V Jubilee Foundation (http://www.rahfo.se/Metamenyn/In-English/) and the Stockholm county council (http://www.sll.se/om-landstinget/Information-in-%20English1/). Chundsell Medicals AB and Ridgeview Instruments AB provided support in the form of salaries for authors ZP and KA, respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.