A potential clinical significance of DAB2IP and SPRY2 transcript variants in prostate cancer

Pathol Res Pract. 2018 Dec;214(12):2018-2024. doi: 10.1016/j.prp.2018.09.019. Epub 2018 Sep 29.

Abstract

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =-0.24 and P = 0.045 ρ =-0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.

Keywords: Benign prostate hyperplasia; DAB2IP; Prostate cancer; SPRY2; Splice variants.

MeSH terms

  • Aged
  • Carcinogenesis / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • DAB2IP protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SPRY2 protein, human
  • ras GTPase-Activating Proteins