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MMP12 可作为肺鳞癌疾病状态和预后的免疫细胞相关标志物。

MMP12 serves as an immune cell-related marker of disease status and prognosis in lung squamous cell carcinoma.

机构信息

Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

出版信息

PeerJ. 2023 Aug 16;11:e15598. doi: 10.7717/peerj.15598. eCollection 2023.

Abstract

BACKGROUND

Worldwide, lung squamous cell carcinoma (LUSC) has wreaked havoc on humanity. Matrix metallopeptidase 12 () plays an essential role in a variety of cancers. This study aimed to reveal the expression, clinical significance, and potential molecular mechanisms of in LUSC.

METHODS

There were 2,738 messenger RNA (mRNA) samples from several multicenter databases used to detect expression in LUSC, and 125 tissue samples were validated by immunohistochemistry (IHC) experiments. Receiver operator characteristic (ROC) curves, Kaplan-Meier curves, and univariate and multivariate Cox regression analyses were used to assess the clinical value of in LUSC. The potential molecular mechanisms of were explored by gene enrichment analysis and immune correlation analysis. Furthermore, single-cell sequencing was used to determine the distribution of in multiple tumor microenvironment cells.

RESULTS

was significantly overexpressed at the mRNA level ( < 0.05, SMD = 3.13, 95% CI [2.51-3.75]), which was verified at the protein level ( < 0.001) by internal IHC experiments. expression could be used to differentiate LUSC samples from normal samples, and overexpression of itself implied a worse clinical prognosis and higher levels of immune cell infiltration in LUSC patients. was involved in cancer development and progression through two immune-related signaling pathways. The high expression of in LUSC might act as an antigen-presenting cell-associated tumor neoantigen and activate the body's immune response.

CONCLUSIONS

expression is upregulated in LUSC and high expression of serves as a risk factor for LUSC patients. may be involved in cancer development by participating in immune-related signaling pathways and elevating the level of immune cell infiltration.

摘要

背景

全球范围内,肺鳞状细胞癌(LUSC)肆虐人类。基质金属蛋白酶 12()在多种癌症中发挥着重要作用。本研究旨在揭示在 LUSC 中的表达、临床意义和潜在的分子机制。

方法

使用来自多个多中心数据库的 2738 个信使 RNA(mRNA)样本检测 LUSC 中表达,并用免疫组织化学(IHC)实验验证了 125 个组织样本。接受者操作特征(ROC)曲线、Kaplan-Meier 曲线、单变量和多变量 Cox 回归分析用于评估在 LUSC 中的临床价值。通过基因富集分析和免疫相关性分析探索的潜在分子机制。此外,单细胞测序用于确定在多种肿瘤微环境细胞中的分布。

结果

在 mRNA 水平上显著过表达(<0.05,SMD = 3.13,95%CI [2.51-3.75]),通过内部 IHC 实验在蛋白质水平上得到验证(<0.001)。表达可用于区分 LUSC 样本和正常样本,并且的过表达本身暗示 LUSC 患者的临床预后更差,免疫细胞浸润水平更高。通过两种免疫相关信号通路参与癌症的发生和发展。LUSC 中表达升高可能作为抗原呈递细胞相关的肿瘤新生抗原并激活机体的免疫反应。

结论

在 LUSC 中表达上调,高表达作为 LUSC 患者的风险因素。可能通过参与免疫相关信号通路和提高免疫细胞浸润水平来参与癌症的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/10439720/6b4f5b024ecd/peerj-11-15598-g001.jpg

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