Eriksen Anne Haahr Mellergaard, Sørensen Flemming Brandt, Andersen Rikke Fredslund, Jakobsen Anders, Hansen Torben Frøstrup
Department of Oncology, Danish Colorectal Cancer Center South, Vejle Hospital, 7100 Vejle, Denmark.
Institute of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark.
Oncol Lett. 2017 Jul;14(1):201-209. doi: 10.3892/ol.2017.6141. Epub 2017 May 9.
Preoperative chemoradiotherapy (CRT) followed by mesorectal excision is the standard treatment for patients with locally advanced rectal cancer (LARC). The balance between treatment efficacy and toxicity is a major issue in the clinical management of these patients. There is a requirement for the identification of predictive molecular biomarkers for the response of patients to CRT. The present study aimed to analyze the association between microRNA (miRNA/miR) expression and treatment efficacy in patients with LARC who were treated with preoperative CRT. From previous clinical trials, 55 patients for the test cohort and 130 patients for the validation cohort met the criteria for the present investigation. Through reverse transcription-quantitative polymerase chain reaction analysis, the expression of miR-21, -31, -125b, -145 and -630 in the diagnostic biopsies was analyzed. The primary endpoint of tumor regression was evaluated according to Mandard's Tumor Regression Grade (TRG) system. In the test cohort, a significant association was identified between low miRNA-145 expression and TRG1+2 (P=0.0003). Similarly, this association was identified in the validation cohort, although it did not reach statistical significance. Furthermore, a significant association between high miRNA-21 expression and TRG1+2 (P=0.035) was observed in the validation cohort. The remaining miRNAs analyzed were not associated with TRG. The results of the present study highlight the clinical importance of miRNAs in LARC and underline the necessity for validation studies in this setting.
术前放化疗(CRT)联合直肠系膜切除术是局部晚期直肠癌(LARC)患者的标准治疗方法。治疗效果与毒性之间的平衡是这些患者临床管理中的一个主要问题。需要鉴定患者对CRT反应的预测性分子生物标志物。本研究旨在分析接受术前CRT治疗的LARC患者中微小RNA(miRNA/miR)表达与治疗效果之间的关联。从先前的临床试验中,55例患者作为测试队列,130例患者作为验证队列,符合本研究的标准。通过逆转录-定量聚合酶链反应分析,分析了诊断性活检中miR-21、-31、-125b、-145和-630的表达。根据Mardard肿瘤消退分级(TRG)系统评估肿瘤消退的主要终点。在测试队列中,低miRNA-145表达与TRG1+2之间存在显著关联(P=0.0003)。同样,在验证队列中也发现了这种关联,尽管未达到统计学意义。此外,在验证队列中观察到高miRNA-21表达与TRG1+2之间存在显著关联(P=0.035)。分析的其余miRNA与TRG无关。本研究结果突出了miRNA在LARC中的临床重要性,并强调了在这种情况下进行验证研究的必要性。