Comprehensive molecular analysis of a four-pyroptosis-gene signature with prognosis and immune landscape in lung adenocarcinoma

Genomics. 2022 May;114(3):110355. doi: 10.1016/j.ygeno.2022.110355. Epub 2022 Mar 29.

Abstract

Pyroptosis plays an important role in tumor immunity. However, the biological behavior and prognostic significance of pyroptosis remain unclear. We identified 41 pyroptosis regulators differently expressed in lung adenocarcinoma (LUAD). All cases of LUAD can be classified into two molecular subtypes using unsupervised clustering algorithm. Using multiple analyses, a four-pyroptosis-gene signature was constructed, and all LUAD patients were categorized as low-risk or high-risk with a longer overall survival (OS) time in the low-risk group(P < 0.001). This signature had power prognosis and stratification which was validated by six independent datasets and clinical subtypes. Besides, this signature showed distinct clinical outcomes, immune landscapes in different risk groups. Moreover, the low-risk group had a higher response against immunotherapy with a lower TIDE score. Importantly, this signature surpassed other biomarkers (TIDE, TMB, PD-L1) in predicting prognosis. Overall, the current study might help with precise prognostic prediction and crucial treatment strategies, eventually promoting tailored therapy for LUAD patients.

Keywords: Biomarker for immunotherapy response; Immune subtype; Immunologic landscape; Lung adenocarcinoma; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Algorithms
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / therapy
  • Prognosis
  • Pyroptosis