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整合素αvβ3/α6β1 在前列腺癌预后和免疫逃逸中的综合分析。

Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer.

机构信息

Department of Urinary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Aging (Albany NY). 2023 Oct 19;15(20):11369-11388. doi: 10.18632/aging.205131.

Abstract

Integrin αvβ3/α6β1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvβ3/α6β1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvβ3/α6β1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvβ3/α6β1 in predicting prognosis, TP53 mutation and immune escape in PCa.

摘要

整合素αvβ3/α6β1在细胞间癌症信息的转导中起着至关重要的作用,但其在前列腺癌(PCa)中的作用仍知之甚少。在这里,我们系统地分析了来自 TCGA 数据库的 495 名 PCa 患者的转录组、单核苷酸多态性(SNP)和临床数据,并在 220 名 GEO 患者中进行了验证,qPCR 用于验证我们患者模型基因的表达。首先,我们发现整合素αvβ3/α6β1与大多数免疫细胞浸润和免疫功能呈负相关,并与 TCGA 患者的不良生存密切相关。然后,我们根据αvβ3/α6β1的表达水平将这些患者分为两组,将两组的差异表达基因与 GEO 数据集进行交叉,并鉴定出 8 个与生化复发相关的基因(BRGs),并在我们的患者中通过 qPCR 进行了验证。接下来,通过应用 LASSO Cox 回归,这些 BRGs 被用于构建一个预后风险模型。我们发现,高危(HR)组的 OS、PFS、生化复发和临床特征均比低危(LR)组差。此外,HR 组主要富集在细胞周期途径中,并且比 LR 组具有更高的 TP53 突变率。更重要的是,HR 组的免疫细胞浸润和免疫功能较低,PD-L1、PD-1 和 CTLA4 的表达较高,免疫排斥评分较高,提示免疫逃逸的可能性较高。这些发现表明整合素αvβ3/α6β1在预测 PCa 患者的预后、TP53 突变和免疫逃逸方面起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6416/10637796/67f2afcbdb6f/aging-15-205131-g001.jpg

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