Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis

Reprod Sci. 2015 Jun;22(6):679-84. doi: 10.1177/1933719114556478. Epub 2014 Oct 30.


Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case-control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-free DNA samples. Quantitative real-time reverse transcription-polymerase chain reaction was performed to determine the expression of KRAS transcripts in eutopic endometrial tissue. Our results suggest that the variant is not associated with the development of endometriosis in Iranian women. We observed higher levels of KRAS messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis compared to controls. Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity.

Keywords: KRAS gene; cell-free DNA; endometriosis; let-7 microRNA; single-nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Binding Sites
  • Case-Control Studies
  • Cell-Free System
  • Endometriosis / diagnosis
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Iran
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Up-Regulation
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • 3' Untranslated Regions
  • KRAS protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • mirnlet7 microRNA, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins