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体细胞突变改变II级浸润性乳腺癌患者的白细胞介素信号通路:一项埃及的研究经验

Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience.

作者信息

Nassar Auhood, Zekri Abdel Rahman N, Elberry Mostafa H, Lymona Ahmed M, Lotfy Mai M, Abouelhoda Mohamed, Youssef Amira Salah El-Din

机构信息

Cancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, Egypt.

Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.

出版信息

Curr Issues Mol Biol. 2022 Nov 26;44(12):5890-5901. doi: 10.3390/cimb44120401.

Abstract

This study aimed to investigate the impact of somatic mutations on various interleukin signaling pathways associated with grade II invasive breast cancer (BC) in Egyptian patients to broaden our understanding of their role in promoting carcinogenesis. Fifty-five grade II invasive BC patients were included in this study. Data for somatic mutations in 45 BC patients were already available from a previous study. Data for somatic mutations of 10 new BC patients were included in the current study. Somatic mutations were identified using targeted next-generation sequencing (NGS) to study their involvement in interleukin signaling pathways. For pathway analysis, we used ingenuity variant analysis (IVA) to identify the most significantly altered pathways. We identified somatic mutations in components of the interleukin-2, interleukin-6, and inter-leukin-7 signaling pathways, including mutations in , and genes. Interestingly, six mutations which were likely to be novel deleterious were identified: two in the gene, two in the gene, and one in each of the and genes. According to IVA analysis, interleukin 2, interleukin 6, and interleukin 7 signaling pathways were the most altered in 34.5%, 29%, and 23.6% of our BC group, respectively. Our multigene panel sequencing analysis reveals that our BC patients have altered interleukin signaling pathways. So, these results highlight the prominent role of interleukins in the carcinogenesis process and suggest its potential role as promising candidates for personalized therapy in Egyptian patients.

摘要

本研究旨在调查体细胞突变对埃及侵袭性II级乳腺癌(BC)患者各种白细胞介素信号通路的影响,以加深我们对其在促进癌变过程中作用的理解。本研究纳入了55例侵袭性II级BC患者。45例BC患者的体细胞突变数据已从先前的研究中获得。本研究纳入了10例新BC患者的体细胞突变数据。使用靶向新一代测序(NGS)鉴定体细胞突变,以研究它们在白细胞介素信号通路中的参与情况。对于通路分析,我们使用 Ingenuity 变异分析(IVA)来识别最显著改变的通路。我们在白细胞介素-2、白细胞介素-6和白细胞介素-7信号通路的组成部分中鉴定出体细胞突变,包括 、 和 基因中的突变。有趣的是,鉴定出六个可能是新的有害突变:两个在 基因中,两个在 基因中, 基因和 基因各有一个。根据IVA分析,在我们的BC组中,白细胞介素2、白细胞介素6和白细胞介素7信号通路分别在34.5%、29%和23.6%的患者中改变最为明显。我们的多基因面板测序分析表明,我们的BC患者的白细胞介素信号通路发生了改变。因此,这些结果突出了白细胞介素在癌变过程中的重要作用,并表明其在埃及患者个性化治疗中作为有前景候选者的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e64/9777163/c9651327cbb0/cimb-44-00401-g001.jpg

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