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Unlocking the potential of senescence-related gene signature as a diagnostic and prognostic biomarker in sepsis: insights from meta-analyses, single-cell RNA sequencing, and in vitro experiments

  • 0Department of Emergency, Panyu Maternal and Child Care Service Centre of Guangzhou, Hexian Memorial Affiliated Hospital of Southern Medical University, Panyu, Guangzhou 511400, Guangdong Province, China.
Aging +

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February 27, 2024

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February 27, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

A new sepsis biomarker using senescence-related genes, TGFBI and MAD1L1, accurately predicts patient outcomes and diagnoses sepsis. This discovery offers a promising tool for precision medicine in sepsis management.

Area Of Science

  • Biomedical research
  • Genomics
  • Sepsis pathogenesis

Background

  • Cellular senescence is implicated in sepsis development.
  • The diagnostic and prognostic utility of senescence-related genes in sepsis is not well-defined.

Purpose Of The Study

  • To identify and validate a senescence-related gene signature for diagnosing and predicting sepsis prognosis.
  • To explore the potential of this signature as a clinical tool for precision medicine.

Main Methods

  • Collected 866 senescence-related genes from CellAge.
  • Utilized Gene Expression Omnibus (GEO) datasets (GSE65682) for training.
  • Applied feature selection methods including LASSO, random forest, and Cox regression.
  • Validated the signature in multiple independent cohorts using various statistical analyses and single-cell RNA sequencing.

Main Results

  • Identified TGFBI and MAD1L1 as key senescence-related genes for sepsis.
  • Developed a risk signature based on TGFBI and MAD1L1 expression, significantly associated with sepsis characteristics and prognosis.
  • The signature demonstrated reliable prognostic prediction across multiple cohorts and robust diagnostic capability distinguishing sepsis from controls.
  • Single-cell RNA sequencing and in vitro experiments confirmed the signature's ability to reflect cellular senescence in monocytes and B cells.

Conclusions

  • A novel senescence-related gene signature (TGFBI and MAD1L1) serves as a valuable prognostic and diagnostic biomarker for sepsis.
  • This signature can aid in uncovering sepsis mechanisms and supports the development of precision medicine strategies.
  • The findings highlight the clinical potential of senescence markers in sepsis management.

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