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

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 (MMP12) plays an essential role in a variety of cancers. This study aimed to reveal the expression, clinical significance, and potential molecular mechanisms of MMP12 in LUSC.

Methods: There were 2,738 messenger RNA (mRNA) samples from several multicenter databases used to detect MMP12 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 MMP12 in LUSC. The potential molecular mechanisms of MMP12 were explored by gene enrichment analysis and immune correlation analysis. Furthermore, single-cell sequencing was used to determine the distribution of MMP12 in multiple tumor microenvironment cells.

Results: MMP12 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 3.13, 95% CI [2.51-3.75]), which was verified at the protein level (p < 0.001) by internal IHC experiments. MMP12 expression could be used to differentiate LUSC samples from normal samples, and overexpression of MMP12 itself implied a worse clinical prognosis and higher levels of immune cell infiltration in LUSC patients. MMP12 was involved in cancer development and progression through two immune-related signaling pathways. The high expression of MMP12 in LUSC might act as an antigen-presenting cell-associated tumor neoantigen and activate the body's immune response.

Conclusions: MMP12 expression is upregulated in LUSC and high expression of MMP12 serves as a risk factor for LUSC patients. MMP12 may be involved in cancer development by participating in immune-related signaling pathways and elevating the level of immune cell infiltration.

Keywords: Clinical value; Gene expression; Immunity; Lung squamous cell carcinoma; MMP12; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung*
  • Carcinoma, Squamous Cell* / genetics
  • Humans
  • Lung
  • Lung Neoplasms* / diagnosis
  • Matrix Metalloproteinase 12 / genetics
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Matrix Metalloproteinase 12
  • MMP12 protein, human

Grants and funding

This study was supported by the Guangxi Zhuang Autonomous Region Medical Health Appropriate Technology Development and Application Promotion Project (NO. S2020031), the Guangxi Medical High-level Key Talents Training “139” Program (NO. 2020), the Guangxi Higher Education Undergraduate Teaching Reform Project (NO. 2022JGA146, NO. 2021JGA142), the Guangxi Educational Science Planning Key Project (NO. 2022xx97, NO. 2021B167), the Guangxi Medical University Key Textbook Construction Project (NO. Gxmuzdjc2223), and the Fund of Future Academic Star of Guangxi Medical University (NO. WLXSZX22112). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.