Conde-Muiño Raquel, Cano Carlos, Sánchez-Martín Victoria, Herrera Antonio, Comino Ana, Medina Pedro P, Palma Pablo, Cuadros Marta
Division of Colon & Rectal Surgery, University Hospital Virgen de las Nieves, Granada, Spain.
Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain.
Oncotarget. 2017 Jul 19;8(47):82294-82302. doi: 10.18632/oncotarget.19393. eCollection 2017 Oct 10.
Administration of chemoradiation before tumor resection has revolutionized the management of locally advanced rectal cancer, but many patients have proven resistant to this preoperative therapy. Our group recently reported a negative correlation between c-Myc gene expression and this resistance. In the present study, integrated analysis of miRNA and mRNA expression profiles was conducted in 45 pre-treatment rectal tumors in order to analyze the expressions of miRNAs and c-Myc and their relationship with clinicopathological factors and patient survival. Twelve miRNAs were found to be differentially expressed by responders and non-responders to the chemoradiation. Functional classification revealed an association between the differentially expressed miRNAs and c-Myc. Quantitative real-time PCR results showed that miRNA-148 and miRNA-375 levels were both significantly lower in responders than in non-responders. Notably, a significant negative correlation was found between miRNA-375 expression and c-Myc expression. According to these findings, miRNA-375 and its targeted c-Myc may be useful as a predictive biomarker of the response to neoadjuvant treatment in patients with locally advanced rectal cancer.
在肿瘤切除前进行放化疗已经彻底改变了局部晚期直肠癌的治疗方式，但许多患者已被证明对这种术前治疗具有抗性。我们团队最近报道了c-Myc基因表达与这种抗性之间存在负相关。在本研究中，对45例治疗前的直肠肿瘤进行了miRNA和mRNA表达谱的综合分析，以分析miRNA和c-Myc的表达及其与临床病理因素和患者生存的关系。发现有12种miRNA在放化疗的反应者和无反应者之间存在差异表达。功能分类显示差异表达的miRNA与c-Myc之间存在关联。定量实时PCR结果显示，反应者中miRNA-148和miRNA-375的水平均显著低于无反应者。值得注意的是，发现miRNA-375表达与c-Myc表达之间存在显著负相关。根据这些发现，miRNA-375及其靶向的c-Myc可能作为局部晚期直肠癌患者新辅助治疗反应的预测生物标志物。
