Lerebours F, Vacher S, Guinebretiere J M, Rondeau S, Caly M, Gentien D, Van Laere S, Bertucci F, de la Grange P, Bièche L, Liang X, Callens C
Département d'Oncologie Médicale, Institut Curie-Hôpital René Huguenin, Saint-Cloud, France.
Service de Génétique, Unité de Pharmacogénomique, Institut Curie, Université Paris Sciences et Lettres, Paris, France.
J Adv Res. 2020 Aug 19;28:77-85. doi: 10.1016/j.jare.2020.08.009. eCollection 2021 Feb.
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.
The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC.
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.
A 5-splice signature (, , , and ) was able to distinguish IBC from non-IBC tumors (p<10). 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). Hb protein expression in epithelial breast tumor cells was confirmed by immunohistochemistry.
IBC has a specific spliced transcript profile and is characterized by hemoglobin gene overexpression that should be investigated in further functional studies.
炎性乳腺癌（IBC）是最具侵袭性的乳腺癌形式，其特征为炎症体征迅速出现，且其分子特征尚未阐明。
本研究的目的是检测炎性乳腺癌特有的基因表达水平和替代性RNA剪接变体。
我们使用Affymetrix外显子芯片进行剪接敏感阵列分析，并对177例炎性乳腺癌患者与183例非炎性乳腺癌患者进行定量逆转录聚合酶链反应分析。我们还评估了所鉴定的候选基因和剪接变体的预后价值。
一个5剪接特征（，，，和）能够区分炎性乳腺癌和非炎性乳腺癌肿瘤（p<10）。这种剪接特征与激素受体阴性非炎性乳腺癌患者无远处转移生存期较差相关（p=0.02），但对炎性乳腺癌无预后价值。与非炎性乳腺癌相比，对炎性乳腺癌中失调基因进行的预测分析确定了一个10基因特征，该特征高度预测炎性乳腺癌表型，并在非炎性乳腺癌中提示预后不良。炎性乳腺癌中最常上调的基因是3种血红蛋白基因，它们能够可靠地区分炎性乳腺癌和非炎性乳腺癌（p<10）。通过免疫组织化学证实了乳腺上皮肿瘤细胞中血红蛋白蛋白的表达。
炎性乳腺癌具有特定的剪接转录谱，其特征为血红蛋白基因过表达，应在进一步的功能研究中进行调查。
