Moreno Elisa Conde, Pascual Alejandro, Prieto-Cuadra Daniel, Laza Val F, Molina-Cerrillo Javier, Ramos-Muñoz Miren Edurne, Rodríguez-Serrano Esperanza Macarena, Soto José Luis, Carrato Alfredo, García-Bermejo María Laura, Guillén-Ponce Carmen
Biomarkers and Therapeutic Targets Group and Core Facility, Ramon y Cajal Research Institute, (IRYCIS), 28034 Madrid, RedinRen, Spain.
Pathology Department, Ramon y Cajal Research Institute, University Hospital, 28034 Madrid, Spain.
Cancers (Basel). 2019 Mar 11;11(3):346. doi: 10.3390/cancers11030346.
microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs. 17 miRNAs were selected for validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) ( = 192) and were further correlated with clinical and histopathological data. We demonstrated that miRNAs associated to Colorectal Cancer (CRC) diagnosis age (over 50s and 60s) included miR-1-3p, miR-23b-3p, miR-27b-3p, miR-143-3p, miR-145-5p and miR-193b-5p. miR-23b-3p and miR-24-3p discriminated between Lynch Syndrome and sporadic CRC. miR-10a-5p, miR-20a-5p, miR-642b and Let-7a-5p were associated to stroma abundance. miR-642b and Let-7a-5p were associated with to peritumoral inflammation abundance. miR-1-3p, miR-143-3p and miR-145-5p correlated with mucinous component. miR-326 correlated with tumour location (right or left sided). miR-1-3p associated with tumour grade. miR-20a-5p, miR-193b-5p, miR-320a, miR-326 and miR-642b-3p associated to tumour stage and progression. Remarkably, we also demonstrated that miR-1-3p and miR-326 expression significantly associated with patient overall survival (OS). Hierarchical clustering and bioinformatics analysis indicated that selected miRNAs could re-classify the patients and work cooperatively, modulating common target genes involved in colorectal cancer key signalling pathways. In conclusion, molecular characterization of CR primary tumours based on miRNAs could lead to more accurate patient reclassification and may be useful for efficient patient management.
微小RNA（miRNA）在结直肠癌（CR）原发肿瘤中的表达有助于进行更精确的分子特征分析。我们鉴定并验证了一种与临床和组织病理学特征相关的miRNA谱，这可能有助于患者分层。使用结直肠癌原发肿瘤石蜡包埋活检组织进行原位杂交阵列，以筛选1436种miRNA。通过定量逆转录聚合酶链反应（qRT-PCR）（n = 192）选择17种miRNA进行验证，并进一步与临床和组织病理学数据相关联。我们证明，与结直肠癌（CRC）诊断年龄（50多岁和60多岁）相关的miRNA包括miR-1-3p、miR-23b-3p、miR-27b-3p、miR-143-3p、miR-145-5p和miR-193b-5p。miR-23b-3p和miR-24-3p可区分林奇综合征和散发性CRC。miR-10a-5p、miR-20a-5p、miR-642b和Let-7a-5p与基质丰度相关。miR-642b和Let-7a-5p与肿瘤周围炎症丰度相关。miR-1-3p、miR-143-3p和miR-145-5p与黏液成分相关。miR-326与肿瘤位置（右侧或左侧）相关。miR-1-3p与肿瘤分级相关。miR-20a-5p、miR-193b-5p、miR-320a、miR-326和miR-642b-3p与肿瘤分期和进展相关。值得注意的是，我们还证明miR-1-3p和miR-326的表达与患者总生存期（OS）显著相关。层次聚类和生物信息学分析表明，所选的miRNA可以对患者进行重新分类，并协同作用，调节参与结直肠癌关键信号通路的共同靶基因。总之，基于miRNA的结直肠癌原发肿瘤分子特征分析可能导致更准确的患者重新分类，并且可能有助于高效的患者管理。
