Ghiarone Thaysa, Hansen Emily, Holaska James M
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ.
Molecular Cell Biology and Neuroscience Program, Rowan-Virtua School of Translational Biomedical Engineering and Sciences, Stratford, NJ.
bioRxiv. 2025 Jul 7:2025.07.03.663032. doi: 10.1101/2025.07.03.663032.
Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression-markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression. These findings highlight emerin as a promising prognostic biomarker and therapeutic target for aggressive breast cancer subtypes.
核异型性是肿瘤侵袭性的关键指标，影响癌细胞的侵袭和转移。Emerin是一种参与核结构的核膜整合蛋白，对维持核完整性很重要。我们之前的研究表明，核膜定位的Emerin表达与乳腺癌侵袭性呈负相关。然而，它没有能力评估Emerin缺失是否与癌症分期、分级、增殖或分子表型相关。在这里，我们分析了243例乳腺癌患者样本中核膜上Emerin的表达情况，这些样本涵盖了各种肿瘤分级、分期和分子表型。我们发现，与正常乳腺组织相比，浸润性导管癌（IDC）、浸润性小叶癌（ILC）和导管原位癌（DCIS）中Emerin的表达显著降低。值得注意的是，Emerin缺失与肿瘤晚期、较高的Ki-67增殖率、人表皮生长因子受体2（HER2）水平升高以及雌激素受体（ER）和孕激素受体（PR）表达降低相关，这些标志物与侵袭性更强的乳腺癌有关。三阴性乳腺癌（TNBC）和其他受体阴性亚型中Emerin的表达持续降低，突出了其在肿瘤去分化和进展中的潜在作用。这些发现强调Emerin是侵袭性乳腺癌亚型有前景的预后生物标志物和治疗靶点。
