From the Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Ireland (Davey, McGuire, Casey, Waldron, Heneghan, McDermott, Lowery, Miller, Kerin).
the School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland (Paganga, Holian, Newell).
J Am Coll Surg. 2023 Feb 1;236(2):317-327. doi: 10.1097/XCS.0000000000000465. Epub 2022 Nov 2.
While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis.
This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3.
A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival.
ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials.
尽管乳腺癌患者的长期预后有所改善，但仍有 20%至 30%的患者会出现复发，因此如何识别这些患者仍是一个挑战。微小 RNA（miRNA）是一种小的非编码分子，可以调节基因表达并影响肿瘤发生。
这项前瞻性、多中心试验（ICORG10/11-NCT01722851）招募了在 8 家爱尔兰中心接受新辅助化疗的患者。使用定量逆转录聚合酶链反应（qRT-PCR）从患者全血中定量测定预定的 miRNA。在诊断时（时间点 1）和新辅助化疗中途（时间点 2 [T2]）进行静脉采样。miRNA 表达谱与无复发生存率（RFS）、无病生存率（DFS）和总生存率相关。使用 R v3.2.3 进行数据分析。
共招募了 124 例患者，中位年龄为 55.0 岁。中位随访时间为 103.1 个月。T2 时 miR-145 表达增加与 RFS 改善相关（风险比 0.00；95%置信区间 [CI] 0.00 至 0.99；p = 0.050）。使用生存回归树分析，相对 miR-145 表达增加大于 0.222 与 RFS 改善相关（p = 0.041）。T2 时 miR-145 表达增加趋势与预测 DFS 改善相关（风险比 0.00；95%CI 0.00 至 1.42；p = 0.067）。使用生存回归树分析，相对 miR-145 表达增加大于 0.222 与 DFS 改善相关（p = 0.012）。没有 miRNA 与总生存率相关。
ICORG10/11 是爱尔兰第一个多中心转化研究试验，评估循环 miRNA 作为预测长期生存的生物标志物，并发现 miR-145 表达增加与早期乳腺癌的更好结局相关。需要在下一代转化研究试验中验证这些发现。
