Department of Clinical Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Clinical Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan
Anticancer Res. 2022 May;42(5):2277-2288. doi: 10.21873/anticanres.15707.
BACKGROUND/AIM: The TP53-signature is a multi-gene signature that can predict TP53 structural mutations. It has presented remarkable ability to predict the prognosis of early-stage breast cancer. However, some samples presented discordance with the signature status and structure status. We aimed to investigate whether the mRNA expression levels or copy number variation (CNV) of MDM2 and CDKN2A influence the TP53-signature-score, subtype classification, and prognosis prediction in TP53 wild-type, luminal type early-stage breast cancer samples.
We selected TP53 wild-type, luminal type early-stage breast cancer samples from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. Then, we analyzed the correlation between the TP53-signature-score and mRNA expression levels or CNV of MDM2 and CDKN2A.
The samples with MDM2 copy number (CN) amplification or those with CDKN2A CN deep deletion presented higher TP53-signature-score. Moreover, samples with MDM2 CN amplification or those with CDKN2A CN deep deletion had more characteristics of the luminal B type. In addition, they showed lower estrogen response early score, which correlated with response to endocrine therapy in breast cancer. However, MDM2 and CDKN2A mRNA expression did not present the same tendency. Furthermore, samples with MDM2 CN amplification or those with CDKN2A CN deep deletion had a worse prognosis in METABRIC cohort.
The MDM2 or CDKN2A CNV may be useful for classifying subtypes and predicting prognosis more accurately in TP53 wild-type, luminal type early-stage breast cancer patients.
背景/目的：TP53 -signature 是一种多基因签名，可以预测 TP53 结构突变。它在预测早期乳腺癌的预后方面表现出了显著的能力。然而，一些样本与签名状态和结构状态存在不一致。我们旨在研究 MDM2 和 CDKN2A 的 mRNA 表达水平或拷贝数变异 (CNV) 是否会影响 TP53 野生型、腔型早期乳腺癌样本中的 TP53-signature 评分、亚型分类和预后预测。
我们从癌症基因组图谱 (TCGA) 和乳腺癌国际分子分类联盟 (METABRIC) 队列中选择了 TP53 野生型、腔型早期乳腺癌样本。然后，我们分析了 TP53-signature 评分与 MDM2 和 CDKN2A 的 mRNA 表达水平或 CNV 之间的相关性。
MDM2 拷贝数 (CN) 扩增或 CDKN2A CN 深度缺失的样本呈现更高的 TP53-signature 评分。此外，MDM2 CN 扩增或 CDKN2A CN 深度缺失的样本具有更多的腔型 B 特征。此外，它们表现出较低的雌激素反应早期评分，这与乳腺癌对内分泌治疗的反应相关。然而，MDM2 和 CDKN2A mRNA 表达没有呈现相同的趋势。此外，MDM2 CN 扩增或 CDKN2A CN 深度缺失的样本在 METABRIC 队列中预后更差。
MDM2 或 CDKN2A 的 CNV 可能有助于更准确地对 TP53 野生型、腔型早期乳腺癌患者进行亚型分类和预后预测。
