A Three-microRNA Signature Predicts Responses to Platinum-Based Doublet Chemotherapy in Patients with Lung Adenocarcinoma

作者：Saito Motonobu; Shiraishi Kouya; Matsumoto Kenji; Schetter Aaron J; Ogata Kawata Hiroko; Tsuchiya Naoto; Kunitoh Hideo; Nokihara Hiroshi; Watanabe Shun ichi; Tsuta Koji; Kumamoto Kensuke; Takenoshita Seiichi; Yokota Jun; Harris Curtis C; Kohno Takashi^*

来源：Clinical Cancer Research, 2014, 20(18): 4784-4793.

DOI：10.1158/1078-0432.CCR-14-1096

Purpose: To examine the clinical utility of intratumor microRNAs (miRNA) as a biomarker for predicting responses to platinum-based doublet chemotherapy in patients with recurring lung adenocarcinoma (LADC).
Experimental Design: The expression of miRNAs was examined in LADC tissues surgically resected from patients treated with platinum-based doublet chemotherapy at the time of LADC recurrence. Microarray-based screening of 904 miRNAs followed by quantitative reverse transcription-PCR-based verification in 40 test cohort samples, including 16 (40.0%) responders, was performed to identify miRNAs that are differentially expressed in chemotherapy responders and nonresponders. Differential expression was confirmed in a validation cohort (n = 63 samples), including 18 (28.6%) responders. An miRNA signature that predicted responses to platinum-based doublet chemotherapy was identified and its accuracy was examined by principal component and support vector machine analyses. Genotype data for the TP53-Arg72Pro polymorphism, which is associated with responses to platinum-based doublet chemotherapy, were subsequently incorporated into the prediction analysis.
Results: A signature comprising three miRNAs (miR1290, miR196b, and miR135a*) enabled the prediction of a chemotherapeutic response (rather than progression-free and overall survival) with high accuracy in both the test and validation cohorts (82.5% and 77.8%). Examination of the latter was performed using miRNAs extracted from archived formalin-fixed paraffin-embedded tissues. Combining this miRNA signature with the TP53-Arg72Pro polymorphism genotype marginally improved the predictive power.
Conclusion: The three-miRNA signature in surgically resected primary LADC tissues may by clinically useful for predicting responsiveness to platinum-based doublet chemotherapy in patients with LADC recurrence.

• 出版日期2014-9-15
• 单位NIH