The let-7 microRNA binding site variant in KRAS as a predictive biomarker for head and neck cancer patients with lymph node metastasis

Pathol Res Pract. 2022 Nov:239:154147. doi: 10.1016/j.prp.2022.154147. Epub 2022 Sep 30.

Abstract

Background: The let-7 family of microRNAs regulate multiple oncogenes including the KRAS gene and has been shown to play a critical role in carcinogenesis. In this study, we aimed to investigate polymorphic alterations of the let-7 miRNA binding site (rs61764370) in the 3'UTR region of the KRAS gene as a predictive biomarker for head and neck cancer (HNC) and to evaluate its association with clinicopathological parameters.

Material and methods: The frequency of the KRAS-LCS6 variant in 216 Turkish HNC' patients and 85 healthy individuals were evaluated. After extracting DNA from whole blood, the variant allele was analyzed by polymerase chain reaction and restriction fragment length polymorphism method. Genotype and allele frequencies were evaluated using the De-Finetti case-control program.

Results: 85.6 % of the patients were wild type, 13 % heterozygous and 1.4 % homozygous variant. Although the KRAS-LCS6 variant was not associated with the risk of HNC (p > 0.05), G homozygous variant allele was found to be significantly associated with HNC patients having lymph node metastasis [T vs G: OR(%95 CI)= 2.370 (1.03-5.41), p = 0.03, χ2 = 4.38]. It was found statistical significance between genotype frequencies and smoker patients [TT vs TG: OR(%95 CI)= 0.357 (0.13-0.97), p = 0.03, χ2 = 4.32] by using De-Finetti analysis. Statistical significance was observed between KRAS-LCS6 genotype frequencies and gender, smoking, alcohol, early/late-stage, lymph node metastasis according to univariate analysis and Cox proportional hazards regression model (p < 0.05).

Conclusion: This is the first study to reveal the relationship between KRAS-LCS6 variant and lymph node metastasis in HNC. The LCS6 variant of the KRAS gene may be a candidate predictor risk biomarker for lymph node metastasis in HNC.

Keywords: head and neck cancer; kras polymorphism; lcs-6; lymph node metastasis; restriction fragment length polymorphism.

MeSH terms

  • Binding Sites
  • Biomarkers
  • Colorectal Neoplasms* / pathology
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Lymphatic Metastasis / genetics
  • MicroRNAs* / genetics
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Proto-Oncogene Proteins p21(ras)
  • MicroRNAs
  • Biomarkers
  • KRAS protein, human