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乳腺癌患者血清α1-抗胰蛋白酶水平及分子分析:一项实验与计算研究

Serum α1-AT Levels and Molecular Analysis in Breast Cancer: An Experimental and Computational Study.

作者信息

Ávalos-Navarro Guadalupe, Bautista-Herrera Luis A, Garibaldi-Ríos Asbiel Felipe, Ramírez-Patiño Ramiro, Gutiérrez-García Marisol, Briseño-Álvarez Perla, Jave-Suárez Luis Felipe, Reyes-Uribe Emmanuel, Gallegos-Arreola Martha Patricia

机构信息

Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotlán 47820, Jalisco, Mexico.

Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías (CUCEI), Universidad de Guadalajara, Blvd. Marcelino García Barragán 1421, Olímpica, Guadalajara 44430, Jalisco, Mexico.

出版信息

Diseases. 2024 Dec 24;13(1):1. doi: 10.3390/diseases13010001.

DOI:10.3390/diseases13010001
PMID:39851465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11765096/
Abstract

BACKGROUND/OBJECTIVES: Breast cancer (BC) is a heterogeneous disease with multifactorial origins, including environmental, genetic, and immunological factors. Inflammatory cytokines, such as alpha 1 antitrypsin (α1-AT), are increased in BC and affect physiological and pathological conditions. This study aimed to evaluate the serum levels of α1-AT and perform a computational analysis of in BC, as well as their association with molecular subtypes and clinical features.

METHODS

For the experimental analysis, we evaluated 255 women with BC and 53 healthy women (HW) in a cross-sectional study. Molecular subtypes were identified by immunohistochemistry and TNM was used for clinical staging. Soluble levels of α1-AT were quantified by ELISA. Computational analysis of expression was performed using GEPIA and cBioPortal.

RESULTS

α1-AT was increased in BC women versus HW (75.8 ng/mL vs. 532.2 ng/mL). Luminal A had higher concentration (547.5 ng/mL) than Triple Negative (TN) (484.1 ng/mL), but the levels were not associated with clinical stage. The computational analysis showed that is overexpressed in BC with differential expression among subtypes; its overexpression is associated with a better prognosis, longer disease-free survival, and overall survival.

CONCLUSIONS

α1-AT levels are increased in women with BC women compared to HW. The Luminal A subtype shows higher soluble protein levels than the TN one. Furthermore, mRNA overexpression in BC is linked to a protective effect.

摘要

背景/目的:乳腺癌(BC)是一种具有多因素起源的异质性疾病,包括环境、遗传和免疫因素。炎症细胞因子,如α1抗胰蛋白酶(α1-AT),在乳腺癌中升高并影响生理和病理状况。本研究旨在评估BC患者血清中α1-AT的水平,并对其进行计算分析,以及它们与分子亚型和临床特征的关联。

方法

在一项横断面研究中,我们评估了255例BC女性患者和53例健康女性(HW)。通过免疫组织化学鉴定分子亚型,采用TNM进行临床分期。采用酶联免疫吸附测定法(ELISA)定量α1-AT的可溶性水平。使用GEPIA和cBioPortal对α1-AT的表达进行计算分析。

结果

与HW相比,BC女性患者的α1-AT水平升高(75.8 ng/mL对532.2 ng/mL)。管腔A型的浓度(547.5 ng/mL)高于三阴性(TN)型(484.1 ng/mL),但这些水平与临床分期无关。计算分析表明,α1-AT在BC中过表达,各亚型间存在差异表达;其过表达与较好的预后、更长的无病生存期和总生存期相关。

结论

与HW相比,BC女性患者的α1-AT水平升高。管腔A型亚型的可溶性蛋白水平高于TN型。此外,BC中α1-AT mRNA的过表达与保护作用相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/e9c68ff46825/diseases-13-00001-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/e4a3dc9001a1/diseases-13-00001-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/48bd1f7865c1/diseases-13-00001-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/74f4bb24f9bf/diseases-13-00001-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/547bd8501686/diseases-13-00001-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/12b8d18b1925/diseases-13-00001-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/e9c68ff46825/diseases-13-00001-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/e4a3dc9001a1/diseases-13-00001-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/48bd1f7865c1/diseases-13-00001-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/74f4bb24f9bf/diseases-13-00001-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/547bd8501686/diseases-13-00001-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/12b8d18b1925/diseases-13-00001-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7653/11765096/e9c68ff46825/diseases-13-00001-g006.jpg

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本文引用的文献

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SERPINA1 promotes the invasion, metastasis, and proliferation of pancreatic ductal adenocarcinoma via the PI3K/Akt/NF-κB pathway.丝氨酸蛋白酶抑制剂A1(SERPINA1)通过PI3K/Akt/NF-κB信号通路促进胰腺导管腺癌的侵袭、转移和增殖。
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具有罕见变异的α-1抗胰蛋白酶PI M杂合子:他们需要临床和功能随访吗?
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