No Tumor Suppressor Role for LKB1 in Prostate Cancer

DNA Cell Biol. 2021 Sep;40(9):1222-1229. doi: 10.1089/dna.2021.0274. Epub 2021 Aug 7.

Abstract

To elucidate the pathogenesis of prostate diseases, following in silico analysis, the LKB1 gene was selected for further investigation. The LKB1 gene has been associated with poor prognosis and is frequently mutated in different types of cancers. In this study, 50 benign prostatic hyperplasia (BPH) and 57 prostate cancer (PCa) tissues, including matched normal tissue for the patients, were analyzed by qRT-PCR and DNA sequencing for LKB1 expression and the mutation profile, respectively. Expression of LKB1 was increased in 60.7% of the PCa tissues compared with noncancerous tissue samples (p ≤ 0.001). However, LKB1 expression was lower when compared with normal tissues in BPH (p = 0.920). Four coding sequence alterations were detected in BPH. Three silent mutations were located in codons 9, 32, and 275 and a missense mutation was observed in codon 384. Six alterations were identified in the intronic regions of the LKB1 gene in both PCa and BPH. Five mutations were observed in both patient groups. A new alteration in intron 6 was observed in a patient with PCa. The LKB1 gene may be associated with benign transformations rather than the tumors in prostate pathogenesis when its expression and mutation status are considered. However, the mechanism of LKB1 in PCa needs further studies.

Keywords: BPH; LKB1; PSA; mutation; prostate cancer.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Hyperplasia* / genetics
  • Prostatic Hyperplasia* / metabolism
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / physiology

Substances

  • Biomarkers, Tumor
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases