Caramés Cristina, Cristóbal Ion, Moreno Víctor, del Puerto Laura, Moreno Irene, Rodriguez María, Marín Juan P, Correa Andrea V, Hernández Roberto, Zenzola Víctor, Hernández Tatiana, León Ana, Martín José I, Sánchez-Fayos Paloma, García-Olmo Damián, Rojo Federico, Goel Ajay, Fernandez-Aceñero María J, García-Foncillas Jesús
Medical Oncology Department, University Hospital "Fundación Jimenez Diaz", Avda. Reyes Católicos-2, 28040, Madrid, Spain.
Int J Colorectal Dis. 2015 Jul;30(7):899-906. doi: 10.1007/s00384-015-2231-9. Epub 2015 May 8.
The treatment of choice for locally advanced rectal cancer is preoperative chemoradiotherapy. Despite half of patients do not respond and suffer unnecessary toxicities and surgery delays, there are no biomarkers to guide preoperative CRT outcome. MicroRNA-21 has been related to acquisition of 5-fluorouracil resistance; however, its potential predictive value of response to preoperative chemoradiotherapy in locally advanced rectal cancer remains unknown.
Nighty-two patients diagnosed with locally advanced rectal cancer who were preoperatively treated with chemoradiotherapy were selected for this study. Moreover, microRNA-21 expression was quantified in formalin-fixed paraffin-embedded biopsies from this cohort, and the results obtained were correlated with clinical and molecular characteristics, pathological response, and outcome.
MicroRNA-21 was found overexpressed in 77.6% cases, and significantly correlated with tumor grade after preoperative chemoradiotherapy (P = 0.013) and with pathological response (P = 0.013). The odds ratio of having miR-21 overexpression and not getting a respond to chemoradiotherapy resulted in 9.75 CI 2.24 to 42. Sensitivity, specificity, negative predictive values, and positive predictive value were 86.6, 60, 42.8, and 92%, respectively. Multivariate analysis confirmed the clinical significance of miR-21 determining preoperative chemoradiotherapy response.
MicroRNA-21 expression efficiently predicts preoperative chemoradiotherapy pathological response in locally advanced rectal cancer.
局部晚期直肠癌的首选治疗方法是术前放化疗。尽管有一半的患者无反应并遭受不必要的毒性反应和手术延迟，但尚无生物标志物可指导术前放化疗的结果。MicroRNA-21与5-氟尿嘧啶耐药性的获得有关；然而，其对局部晚期直肠癌术前放化疗反应的潜在预测价值仍不清楚。
本研究选取了92例诊断为局部晚期直肠癌且接受术前放化疗的患者。此外，对该队列中福尔马林固定石蜡包埋活检组织中的MicroRNA-21表达进行定量，并将所得结果与临床和分子特征、病理反应及预后相关联。
发现MicroRNA-21在77.6%的病例中过表达，且与术前放化疗后的肿瘤分级显著相关（P = 0.013）以及与病理反应相关（P = 0.013）。MicroRNA-21过表达且对放化疗无反应的优势比为9.75，置信区间为2.24至42。敏感性、特异性、阴性预测值和阳性预测值分别为86.6%、60%、42.8%和92%。多变量分析证实了MicroRNA-21对术前放化疗反应的临床意义。
MicroRNA-21表达可有效预测局部晚期直肠癌术前放化疗的病理反应。
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