Introduction

Inflammatory Breast Cancer (IBC) is the most aggressive form of breast carcinoma characterized by rapid onset of inflammatory signs and its molecular fingerprint has not yet been elucidated.

Objectives

The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC.

Methods

W e performed splice-sensitive array profiling using Affymetrix Exon Array and quantitative RT-PCR analyses in 177 IBC compared to 183 non-IBC. We also assessed the prognostic value of the identified candidate genes and splice variants.

Results

A 5-splice signature (HSPA8, RPL10, RPL4, DIDO1 and EVL) was able to distinguish IBC from non-IBC tumors (p<10^-7). This splice signature was associated with poor metastasis-free survival in hormone receptor-negative non-IBC (p=0.02), but had no prognostic value in IBC. PAM analysis of dysregulated genes in IBC compared to non-IBC identified a 10-gene signature highly predictive of IBC phenotype and conferring a poor prognosis in non-IBC. The genes most commonly upregulated in IBC were 3 hemoglobin genes able to reliably discriminate IBC from non-IBC (p<10^-4). Hb protein expression in epithelial breast tumor cells was confirmed by immunohistochemistry.

Conclusion

IBC has a specific spliced transcript profile and is characterized by hemoglobin gene overexpression that should be investigated in further functional studies.

中文翻译：

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血红蛋白过度表达和剪接特征是炎性乳腺癌的新特征？

介绍

炎症性乳腺癌 (IBC) 是最具侵袭性的乳腺癌形式，其特征是炎症体征迅速发作，其分子指纹尚未阐明。

目标

本研究的目的是检测 IBC 特异性的基因表达水平和替代 RNA 剪接变体。

方法

我们使用 Affymetrix 外显子阵列和定量 RT-PCR 分析对 177 个 IBC 与 183 个非 IBC 进行了剪接敏感阵列分析。我们还评估了已鉴定的候选基因和剪接变体的预后价值。

结果

5 剪接特征（HSPA8、RPL10、RPL4、DIDO1和EVL）能够区分 IBC 和非 IBC 肿瘤（p<10 ^-7）。这种剪接特征与激素受体阴性非 IBC 中较差的无转移存活率相关（p = 0.02），但在 IBC 中没有预后价值。与非 IBC 相比，IBC 中失调基因的 PAM 分析确定了一个 10 基因特征，高度预测 IBC 表型并赋予非 IBC 不良预后。在 IBC 中最常见上调的基因是 3 个能够可靠地区分 IBC 与非 IBC 的血红蛋白基因 (p<10 ^-4 )。通过免疫组织化学证实了上皮乳腺肿瘤细胞中 Hb 蛋白的表达。

结论

IBC 具有特定的剪接转录谱，其特点是血红蛋白基因过表达，应在进一步的功能研究中进行研究。