Department of Otorhinolaryngology-Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Türkiye.
Pathol Res Pract. 2022 Nov;239:154147. doi: 10.1016/j.prp.2022.154147. Epub 2022 Sep 30.
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.
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.
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).
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.
let-7 家族 miRNA 调控包括 KRAS 基因在内的多个癌基因，在肿瘤发生中发挥着关键作用。本研究旨在探讨 KRAS 基因 3'UTR 区 let-7 结合位点（rs61764370）多态性改变作为头颈部癌症（HNC）的预测生物标志物，并评估其与临床病理参数的关系。
评估了 216 例土耳其 HNC 患者和 85 例健康个体 KRAS-LCS6 变异的频率。从全血中提取 DNA 后，通过聚合酶链反应和限制性片段长度多态性方法分析变异等位基因。使用 De-Finetti 病例对照程序评估基因型和等位基因频率。
85.6%的患者为野生型，13%为杂合子，1.4%为纯合子变异。虽然 KRAS-LCS6 变异与 HNC 风险无关（p>0.05），但 G 纯合子变异等位基因与 HNC 患者淋巴结转移显著相关[T 对 G：OR（%95CI）=2.370（1.03-5.41），p=0.03，χ2=4.38]。De-Finetti 分析显示基因型频率与吸烟者之间存在统计学意义[TT 对 TG：OR（%95CI）=0.357（0.13-0.97），p=0.03，χ2=4.32]。单因素分析和 Cox 比例风险回归模型显示，KRAS-LCS6 基因型频率与性别、吸烟、饮酒、早期/晚期、淋巴结转移均有统计学意义（p<0.05）。
这是第一项揭示 KRAS-LCS6 变异与 HNC 淋巴结转移之间关系的研究。KRAS 基因 LCS6 变异可能是 HNC 淋巴结转移的候选风险预测生物标志物。
