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基质金属蛋白酶2(MMP2)、细丝蛋白A(FLNA)和丝切蛋白1(CFL1)的低表达与浸润性微乳头状乳腺癌的良好预后相关。

Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.

作者信息

Wang Yidi, Zhang Jingyi, Wang Ying, Liu Yu, Shi Bohui, Li Xiaoqian, He Jianjun, Zhang Huimin

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China; Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

出版信息

Gene. 2025 Mar 10;940:149192. doi: 10.1016/j.gene.2024.149192. Epub 2024 Dec 25.

DOI:10.1016/j.gene.2024.149192
PMID:39724992
Abstract

PURPOSE

Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.

METHODS

Through the SEER database, we compared patients survival outcomes with invasive micropapillary carcinoma versus invasive ductal carcinoma, and developed a nomogram to predict the overall survival of the former group. We explored gene profiles of invasive micropapillary carcinoma in the GEO database. Hub genes were identified as the top ten genes in the PPI network with the highest degrees of connectivity, and three of them were selected for validation by immunohistochemistry.

RESULTS

Invasive micropapillary carcinoma patients had better overall survival and breast cancer-specific survival than invasive ductal carcinoma patients did. Multivariate analysis revealed age, marital status, TN stage, ER status, and chemotherapy as independent prognostic factors for invasive micropapillary carcinoma patients, which were used to construct a nomogram with good performance. A total of 294 DEGs were identified, with ten hub genes, including MMP2, FLNA and CFL1, which were expressed at lower levels in invasive micropapillary carcinoma patients than in invasive ductal carcinoma patients, indicating favorable outcomes.

CONCLUSIONS

Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.

摘要

目的

尽管浸润性微乳头状癌具有公认的侵袭性临床表现,但与乳腺浸润性导管癌相比,其预后仍存在争议。本回顾性研究旨在探讨浸润性微乳头状癌的预后及潜在分子机制。

方法

通过监测、流行病学与最终结果(SEER)数据库,我们比较了浸润性微乳头状癌与浸润性导管癌患者的生存结局,并绘制了列线图以预测前者的总生存期。我们在基因表达综合数据库(GEO)中探索了浸润性微乳头状癌的基因谱。枢纽基因被确定为蛋白质-蛋白质相互作用(PPI)网络中连接度最高的前十位基因,并选择其中三个通过免疫组织化学进行验证。

结果

浸润性微乳头状癌患者的总生存期和乳腺癌特异性生存期均优于浸润性导管癌患者。多因素分析显示年龄、婚姻状况、TN分期、雌激素受体(ER)状态和化疗是浸润性微乳头状癌患者的独立预后因素,这些因素被用于构建性能良好的列线图。共鉴定出294个差异表达基因(DEG),包括基质金属蛋白酶2(MMP2)、细丝蛋白A(FLNA)和丝切蛋白1(CFL1)在内的十个枢纽基因在浸润性微乳头状癌患者中的表达水平低于浸润性导管癌患者,提示预后良好。

结论

浸润性微乳头状癌患者的预后通常优于浸润性导管癌患者,这可能归因于前者促癌基因的低表达;然而,其潜在机制仍需进一步研究。

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