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乳腺癌进展、预后相关基因及新型治疗靶点的计算机模拟鉴定

In Silico Identification of Genes Associated with Breast Cancer Progression and Prognosis and Novel Therapeutic Targets.

作者信息

Uchida Shiro, Sugino Takashi

机构信息

Division of Diagnostic Pathology, Kikuna Memorial Hospital, Yokohama 222-0011, Japan.

Pathology Division, Shizuoka Cancer Center, Shizuok 411-8777, Japan.

出版信息

Biomedicines. 2022 Nov 21;10(11):2995. doi: 10.3390/biomedicines10112995.

Abstract

Molecular mechanisms underlying breast cancer (BC) progression are complex and remain unclear. In this study, we used bioinformatic tools to identify genes associated with tumor progression mechanisms and novel therapeutic targets in BC. We identified genes with stepwise upregulated expression overlapping between the T and N stages during BC progression using LinkedOmics. We compared the expression level of each gene in BC tissues with that in normal breast tissues and evaluated differences in expression in their intrinsic subtypes and their prognostic value using UALCAN and GEPIA2. We also investigated the dependency of BC cell lines on these genes and whether they are potential therapeutic targets using DepMap. SPDEF, TRIM3, ABCB9, HSPB1, RHBG, SPINT1, EPN3, LRFN2, and PRPH were found to be involved in BC progression. High expression of ABCB9 and SPINT1 was associated with a poor prognosis. SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH were found to be essential for survival in some BC cell lines (gene effect score < −0.5). PRPH was newly discovered to be involved in the progression of BC and the growth and survival of BC cell lines. Hence, SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH may serve as novel potential therapeutic targets in BC.

摘要

乳腺癌(BC)进展的分子机制复杂且尚不清楚。在本研究中,我们使用生物信息学工具来识别与BC肿瘤进展机制相关的基因和新的治疗靶点。我们使用LinkedOmics识别了在BC进展过程中T期和N期之间表达逐步上调且重叠的基因。我们将BC组织中每个基因的表达水平与正常乳腺组织中的表达水平进行比较,并使用UALCAN和GEPIA2评估其内在亚型中的表达差异及其预后价值。我们还使用DepMap研究了BC细胞系对这些基因的依赖性以及它们是否为潜在的治疗靶点。发现SPDEF、TRIM3、ABCB9、HSPB1、RHBG、SPINT1、EPN3、LRFN2和PRPH参与了BC进展。ABCB9和SPINT1的高表达与不良预后相关。发现SPDEF、TRIM3、ABCB9、RHBG、SPINT1和PRPH对某些BC细胞系的存活至关重要(基因效应评分<−0.5)。新发现PRPH参与BC的进展以及BC细胞系的生长和存活。因此,SPDEF、TRIM3、ABCB9、RHBG、SPINT1和PRPH可能成为BC新的潜在治疗靶点。

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