心力衰竭伴疼痛患者的差异基因表达。

Differential Gene Expression Among Patients With Heart Failure Experiencing Pain.

出版信息

Nurs Res. 2023;72(3):175-184. doi: 10.1097/NNR.0000000000000648. Epub 2023 Feb 26.

PMID:36920122

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10121868/

Abstract

BACKGROUND

Chronic pain is frequently experienced by patients with heart failure (HF) and is associated with higher mortality, higher symptom burden, and worsened health-related quality of life. However, the genomic mechanisms underlying chronic pain in HF are understudied. Building an understanding of the mechanistic underpinnings of pain may inform novel interventions.

OBJECTIVE

The objective was to identify genes associated with pain from messenger RNA sequence data collected from patients with HF with and without pain.

METHODS

The current study analyzed data from 40 patients with HF previously enrolled in a clinical trial. Pain presence was measured using the Health Utilities Index Mark-3. Genes were tested for differential expression using DESeq2, and differentially expressed genes were analyzed for protein-protein interaction (PPI) and relevant ontological pathways using Metascape. Genes located within the core of the PPI network were considered key in disease-relevant biological pathways. Differentially expressed genes within this PPI network were reviewed in existing literature to narrow down candidate genes of interest. These target genes of interest were reanalyzed in a second sample of 24 patients with HF using validation quantitative polymerase chain reaction.

RESULTS

A total of 334 genes (279 upregulated, 55 downregulated) were differentially expressed between patients with and without pain in the primary sample of 40. These genes were largely aligned with neutrophil degranulation pathways. Seven genes of interest were identified from a core network of 15 co-expressed genes in the PPI network and existing literature. Three of these seven genes, matrix metallopeptidase 8 ( MMP8 ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and neutrophil defensin 3 ( DEFA3 ), were upregulated in patients with pain versus without pain in both the primary and validation samples. All seven genes of interest are involved in immune, inflammatory, and atherosclerotic processes.

DISCUSSION

These results identify potential genes that may play a mechanistic role in chronic pain in HF. Further research is needed to evaluate these potential genes among clearly delineated pain phenotypes.

摘要

背景

慢性疼痛是心力衰竭（HF）患者经常经历的一种症状，与更高的死亡率、更高的症状负担和更差的健康相关生活质量相关。然而，HF 中慢性疼痛的基因组机制仍研究不足。了解疼痛的机制基础可以为新的干预措施提供信息。

目的

本研究旨在从 HF 伴有和不伴有疼痛的患者的信使 RNA 序列数据中识别与疼痛相关的基因。

方法

本研究分析了先前纳入临床试验的 40 例 HF 患者的数据。使用健康效用指数 Mark-3 测量疼痛的存在。使用 DESeq2 测试基因的差异表达，使用 Metascape 分析差异表达基因的蛋白质-蛋白质相互作用（PPI）和相关本体途径。被认为与疾病相关生物途径相关的 PPI 网络核心基因被认为是关键基因。在现有文献中回顾该 PPI 网络内的差异表达基因，以缩小感兴趣的候选基因的范围。使用验证定量聚合酶链反应在第二个 24 例 HF 患者的样本中重新分析这些感兴趣的靶基因。

结果

在原发性 40 例样本中，疼痛患者和无疼痛患者之间共有 334 个基因（279 个上调，55 个下调）存在差异表达。这些基因主要与嗜中性粒细胞脱颗粒途径相关。在 PPI 网络中 15 个共表达基因的核心网络中确定了 7 个感兴趣的基因，这些基因与现有文献中的基因基本一致。在原发性和验证样本中，这 7 个感兴趣的基因中有 3 个（基质金属蛋白酶 8 [MMP8]、前蛋白转化酶枯草溶菌素/激肽释放酶 9 [PCSK9]和中性粒细胞防御素 3 [DEFA3]）在疼痛患者中上调，而在无疼痛患者中下调。这 7 个感兴趣的基因都参与免疫、炎症和动脉粥样硬化过程。