胸腺素 β15A（TMSB15A）是三阴性乳腺癌化疗反应的预测因子。

Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.

机构信息

Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

出版信息

Br J Cancer. 2012 Nov 20;107(11):1892-900. doi: 10.1038/bjc.2012.475. Epub 2012 Oct 18.

BACKGROUND

Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed.

METHODS

Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383).

RESULTS

A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro.

CONCLUSION

In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.

背景

迫切需要能够预测乳腺癌新辅助化疗（NACT）病理完全缓解（pCR）的生物标志物。

方法

采用一种用于检测 HER2 阴性乳腺癌预测性生物标志物的训练/验证方法，对四个独立队列的治疗前核心活检进行了研究：在两个队列的新鲜冷冻样本中分析了基因阵列数据（n=86 和 n=55）。在两项新辅助 III 期试验（GeparTrio，n=212 和 GeparQuattro，n=383）的福尔马林固定、石蜡包埋（FFPE）样本中进行了定量逆转录聚合酶链反应（qRT-PCR）。

结果

在两个新鲜冷冻队列中，胸腺素β 15（TMSB15A）基因表达具有很强的预测能力（P<0.0001；P<0.0042）。在 GeparTrio FFPE 训练队列中，在三阴性乳腺癌（TNBC）中，TMSB15A 表达与 pCR 之间存在显著的线性相关性（n=61，P=0.040）。然后定义了一个截断点，将 TNBC 分为低表达和高表达组（pCR 率为 16.0% vs 47.2%）。TMSB15A mRNA 水平的线性相关性（P=0.017）和预定义的截断点在 GeparQuattro 的 134 例 TNBC 中得到了验证（pCR 率为 36.8% vs 17.0%，P=0.020）。在 GeparTrio 和 GeparQuattro 的 luminal 癌中未观察到显著的预测能力。