文章：

基于PRLR基因型、表达及转录网络调控的乳腺癌队列中辅助放疗预后差异研究

Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based onPRLRGenotypes, Expression, and Transcriptional Network Regulation

原文发布日期：17 July 2025

DOI: 10.3390/cancers17142378

类型: Article

开放获取: 是

英文摘要：

Background:Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response.Methods:The prognostic impact of 20PRLRsingle nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n= 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors.Results:Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one ‘rare’. Patients carrying combined genotype AG/GG/TT/CC/TC or ‘rare’ combinations derived greater benefits from radiotherapy than other patient groups (both HRadj≤ 0.29, Bonferroni-adjustedPint≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that threePRLRSNPs were associated with decreasedPRLRexpression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated thatPRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity.Conclusions:PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients.

摘要翻译： 

背景：催乳素受体（PRLR）信号通路影响母乳喂养，并可能影响乳腺癌治疗反应。方法：本研究评估了20个PRLR单核苷酸多态性（SNPs）对原发性乳腺癌患者（n=1701，2002–2016年，瑞典）在不同辅助治疗组中的预后影响。通过Illumina OncoArray平台对基因组DNA进行基因分型，并进行了长达15年的随访生存分析。研究根据不同辅助治疗方式（化疗、放疗、他莫昔芬和芳香化酶抑制剂）建立了交互作用模型，并对潜在混杂因素进行了调整。结果：五个SNPs（rs7734558、rs6860397、rs2962101、rs7732013和rs4703503）显示出与放疗的交互作用，并用于构建七种组合基因型：六种独特型和一种“罕见”型。携带组合基因型AG/GG/TT/CC/TC或“罕见”组合的患者从放疗中获益大于其他患者组（HRadj≤0.29，Bonferroni校正Pint≤0.039）。表达数量性状位点（eQTL）分析显示，三个PRLR SNPs与PRLR表达降低相关。为探索SNP的潜在影响，在METABRIC队列中分析了基因表达和转录网络，结果表明PRLR低表达肿瘤与DNA修复信号减弱和抗肿瘤免疫增强相关。结论：PRLR作为乳腺癌患者放疗相关的潜在药物基因组学生物标志物值得进一步评估。

原文链接：

Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based onPRLRGenotypes, Expression, and Transcriptional Network Regulation