Sirek Tomasz, Sirek Agata, Opławski Marcin, Boroń Dariusz, Chalcarz Michał, Ossowski Piotr, Dziobek Konrad, Zmarzły Nikola, Strojny Damian, Grabarek Beniamin Oskar
Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, Katowice, Poland.
Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Biała, Bielsko-Biala, Poland.
Front Oncol. 2024 Aug 29;14:1407538. doi: 10.3389/fonc.2024.1407538. eCollection 2024.
Disparities in estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67 proliferation indices facilitate the categorization of breast cancer into four principal subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Preclinical studies investigating the therapeutic potential of histaminergic system targeting in breast cancer have shown promising results. This study aimed to assess the expression profiles of messenger ribonucleic acid (mRNA) and micro RNA (miRNA) related to the histaminergic system in five subtypes of breast cancer among Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2-, n =100; HER2+, n= 96), HER2+ (n = 36), and TNBC (n = 43). They underwent surgery during which the tumor tissue was removed along with a margin of healthy tissue (control material). Molecular analysis included the determination of a microarray profile of mRNAs and miRNAs associated with the histaminergic system, real-time polymerase chain reaction preceded by reverse transcription of selected genes, and determination of histamine receptors (human histamine H1 receptor [HRH1], human histamine H2 receptor [HRH2], and human histamine H4 receptor [HRH4]) using an enzyme-linked immunosorbent assay. Statistical analysis was performed with statistical significance at p < 0.05. Nine mRNAs were significantly differentiated in breast cancer sections, regardless of subtype, compared to control samples: , , histamine N-methyltransferase , 5-hydroxytryptamine receptor 6 (, endothelin 1 (, endothelin receptor type A , adenosine deaminase , solute carrier family 22 member 3 ( Predictive analysis showed that hsa-miR-34a potentially regulates expression, whereas hsa-miR-3140-5p and hsa-miR-4251 potentially affect expression. In contrast, and expression were regulated by hsa-miR-1-3p. The expression of is potentially regulated by one miRNA, hsa-miR-382, whereas expression is regulated by two miRNA molecules: hsa-miR-34a and hsa-miR-16. In contrast, hsa-miR-650 is involved in the regulation of expression, whereas hsa-miR-1275 potentially interacts with three mRNAs: , , and . Molecular analysis confirmed that the selected mRNA and miRNA transcripts could be promising molecular markers and therapeutic targets.
雌激素受体（ER）、孕激素受体、人表皮生长因子受体2（HER2）及Ki67增殖指数的差异有助于将乳腺癌分为四种主要亚型：腔面A型、腔面B型、HER2阳性型及三阴性乳腺癌（TNBC）。针对组胺能系统靶向治疗乳腺癌潜力的临床前研究已显示出有前景的结果。本研究旨在评估波兰女性乳腺癌五种亚型中与组胺能系统相关的信使核糖核酸（mRNA）和微小RNA（miRNA）的表达谱。研究纳入了乳腺癌五种亚型的患者：腔面A型（n = 130）、腔面B型（n = 196，包括HER2阴性型，n = 100；HER2阳性型，n = 96）、HER2阳性型（n = 36）及TNBC（n = 43）。她们接受了手术，术中切除肿瘤组织及切缘健康组织（对照材料）。分子分析包括测定与组胺能系统相关的mRNA和miRNA的微阵列图谱、对选定基因进行逆转录后进行实时聚合酶链反应，以及使用酶联免疫吸附测定法测定组胺受体（人组胺H1受体[HRH1]、人组胺H2受体[HRH2]及人组胺H4受体[HRH4]）。采用p < 0.05的统计学显著性进行统计分析。与对照样本相比，无论亚型如何，乳腺癌切片中有9种mRNA存在显著差异： ， ，组胺N - 甲基转移酶，5 - 羟色胺受体6（ ，内皮素1（ ，A型内皮素受体 ，腺苷脱氨酶，溶质载体家族22成员3（ 预测分析表明，hsa - miR - 34a可能调节 表达，而hsa - miR - 3140 - 5p和hsa - miR - 4251可能影响 表达。相反， 和 表达受hsa - miR - 1 - 3p调节。 的表达可能受一种miRNA，hsa - miR - 382调节，而 表达受两种miRNA分子调节：hsa - miR - 34a和hsa - miR - 16。相反，hsa - miR - 650参与 表达的调节，而hsa - miR - 1275可能与三种mRNA相互作用： ， ，和 。分子分析证实，选定的mRNA和miRNA转录本可能是有前景的分子标志物和治疗靶点。
