Data from: The clinical significance and molecular features of the spatial tumor shapes in breast cancers

Each breast cancer has its unique spatial shape, but the clinical importance and the underlying mechanism for the three-dimensional tumor shapes are mostly unknown. We collected the data on the three-dimensional tumor size and tumor volume data of invasive breast cancers from 2,250 patients who underwent surgery between Jan 2000 and Jul 2007. The degree of tumor eccentricity was estimated by using the difference between the spheroid tumor volume and ellipsoid tumor volume (spheroid-ellipsoid discrepancy, SED). In 41 patients, transcriptome and exome sequencing data obtained. Estimation of more accurate tumor burden by calculating ellipsoid tumor volumes did not improve the outcome prediction when compared to the traditional longest diameter measurement. However, the spatial tumor eccentricity, which was measured by SED, showed significant variation between the molecular subtypes of breast cancer. Additionally, the degree of tumor eccentricity was associated with well-known prognostic factors of breast cancer such as tumor size and lymph node metastasis. Transcriptome data from 41 patients showed significant association between MMP13 and spatial tumor shapes. Network analysis and analysis of TCGA gene expression data suggest that MMP13 is regulated by ERBB2 and S100A7A. The present study validates the usefulness of the current tumor size method in determining tumor stages. Furthermore, we show that the tumors with high eccentricity are more likely to have aggressive tumor characteristics. Genes involved in the extracellular matrix remodeling can be candidate regulators of the spatial tumor shapes in breast cancer.

每一例乳腺癌均具有独特的空间形态，但三维肿瘤形态的临床意义与潜在机制大多尚未明确。本研究收集了2000年1月至2007年7月期间接受手术治疗的2250例浸润性乳腺癌患者的三维肿瘤尺寸与肿瘤体积数据。肿瘤偏心率通过球体肿瘤体积与椭球体肿瘤体积的差值进行估算（球体-椭球体差值，spheroid-ellipsoid discrepancy, SED）。对其中41例患者，获取了转录组与外显子组测序数据。相较于传统的最长径测量法，通过计算椭球体肿瘤体积以估算更准确的肿瘤负荷，并未提升预后预测效能。然而，通过SED测算的空间肿瘤偏心率在乳腺癌各分子亚型间存在显著差异。此外，肿瘤偏心率与乳腺癌已知的预后因素（如肿瘤尺寸、淋巴结转移）显著相关。对41例患者的转录组数据分析显示，MMP13与肿瘤空间形态存在显著关联。通过网络分析与TCGA基因表达数据分析发现，MMP13受ERBB2与S100A7A调控。本研究证实了当前肿瘤尺寸测量方法在肿瘤分期判定中的应用价值。此外，本研究还发现，高偏心率的肿瘤更易表现出侵袭性肿瘤特征。参与细胞外基质重塑的基因可作为乳腺癌空间形态的潜在调控因子。