Lagendijk Mirelle, Sadaatmand Sepideh, Koppert Linetta B, Tilanus-Linthorst Madeleine M A, de Weerd Vanja, Ramírez-Moreno Raquel, Smid Marcel, Sieuwerts Anieta M, Martens John W M
Department of Surgical Oncology, Erasmus MC Cancer Institute, EA 3075, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, EA 3075, Rotterdam, The Netherlands.
Oncotarget. 2018 May 11;9(36):24335-24346. doi: 10.18632/oncotarget.25262.
MicroRNAs (miRs) are small RNA molecules, influencing messenger RNA (mRNA) expression and translation, and are readily detectable in blood. Some have been reported as potential breast cancer biomarkers. This study aimed to identify and validate miRs indicative of breast cancer.
Based on the discovery and literature, 18 potentially informative miRs were quantified in the validation cohort. Irrespective of patient and tumour characteristics, was significantly upregulated in the malignant compared to benign patients (1.26 fold, = 0.005) and therefore validated as potential biomarker. In the validation cohort literature-based levels were higher in malignant patients as well (1.53 fold, = 0.011). Two miRs differentiated benign wildtype from benign mutation carriers and an additional 8 miRs differentiated metastastic ( = 8) from non-metastatic ( = 41) cases in the validation cohort.
Pre-treatment plasma samples were collected of patients with benign breast disease and breast cancer and divided over a discovery ( = 31) and validation ( = 84) cohort. From the discovery cohort miRs differentially expressed between benign and malignant cases were identified using a 2,000-miR microarray. Literature-based miRs differentiating benign from malignant disease were added. Using RT-qPCR, their expression was investigated in a validation cohort consisting of pre-treatment benign, malignant and metastatic samples. Additionally, benign and malignant cases were compared to benign and malignant cases of -mutation carriers.
Plasma microRNA levels differed between patients with and without breast cancer, between benign disease from wildtype and -mutation carriers and between breast cancer with and without metastases. was validated as a potential biomarker for breast cancer.
微小RNA（miRs）是小分子RNA分子，可影响信使核糖核酸（mRNA）的表达和翻译，且易于在血液中检测到。一些miRs已被报道为潜在的乳腺癌生物标志物。本研究旨在识别和验证指示乳腺癌的miRs。
基于发现和文献，在验证队列中对18种潜在信息丰富的miRs进行了定量。无论患者和肿瘤特征如何，与良性患者相比，恶性患者中的[具体miR名称未给出]显著上调（1.26倍，P = 0.005），因此被验证为潜在生物标志物。在验证队列中，基于文献的[具体miR名称未给出]水平在恶性患者中也更高（1.53倍，P = 0.011）。在验证队列中，两种miRs区分了良性野生型与良性[具体基因名称未给出]突变携带者，另外8种miRs区分了转移性（n = 8）与非转移性（n = 41）病例。
收集了患有良性乳腺疾病和乳腺癌患者的治疗前血浆样本，并分为发现队列（n = 31）和验证队列（n = 84）。使用2000-miR微阵列从发现队列中鉴定出良性和恶性病例之间差异表达的miRs。添加了基于文献区分良性与恶性疾病的miRs。使用逆转录定量聚合酶链反应（RT-qPCR），在由治疗前良性、恶性和转移性样本组成的验证队列中研究它们的表达。此外，将良性和恶性病例与[具体基因名称未给出]突变携带者的良性和恶性病例进行了比较。
乳腺癌患者与非乳腺癌患者之间、野生型和[具体基因名称未给出]突变携带者的良性疾病之间以及有转移和无转移的乳腺癌之间，血浆微小RNA水平存在差异。[具体miR名称未给出]被验证为乳腺癌的潜在生物标志物。
