Prognostic, immunity, stemness, and anticancer drug sensitivity characterization of pyroptosis related genes in non‐small cell lung cancer

Cong Xu; Hongming Ma; Jiawen Chen; Xincheng Li; Zhina Wang; Bin Hu; Nan Zhang; Fanjie Meng

doi:10.1111/1759-7714.15180

Thoracic Cancer (Jan 2024)

Prognostic, immunity, stemness, and anticancer drug sensitivity characterization of pyroptosis related genes in non‐small cell lung cancer

Cong Xu,
Hongming Ma,
Jiawen Chen,
Xincheng Li,
Zhina Wang,
Bin Hu,
Nan Zhang,
Fanjie Meng

Affiliations

Cong Xu: Department of Thoracic Surgery Peking University Shougang Hospital Beijing China
Hongming Ma: Department of Respiratory and Critical Care Emergency General Hospital Beijing China
Jiawen Chen: Beijing Institute of Lifeomics Beijing China
Xincheng Li: Department of Thoracic Surgery Beijing Institute of Respiratory Medicine and Beijing Chao‐Yang Hospital, Capital Medical University Beijing China
Zhina Wang: Department of Respiratory and Critical Care Emergency General Hospital Beijing China
Bin Hu: Department of Thoracic Surgery Beijing Institute of Respiratory Medicine and Beijing Chao‐Yang Hospital, Capital Medical University Beijing China
Nan Zhang: Department of Respiratory and Critical Care Emergency General Hospital Beijing China
Fanjie Meng: Department of Thoracic Surgery Beijing Institute of Respiratory Medicine and Beijing Chao‐Yang Hospital, Capital Medical University Beijing China

DOI: https://doi.org/10.1111/1759-7714.15180
Journal volume & issue: Vol. 15, no. 3
pp. 215 – 226

Abstract

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Abstract Background Pyroptosis plays a pivotal role in the tumor immune microenvironment (TME) dynamics, particularly in non‐small cell lung cancer (NSCLC). The aim of our study was to explore its effects on tumor progression, TME patterns, and the efficacy of therapeutic interventions in NSCLC. Methods Our investigation encompassed a thorough analysis of pyroptosis‐related genes (PRGs), integrating immunohistochemistry (IHC) data, TME characteristics, stemness indices, and anticancer drug sensitivities. We aimed to analyze mRNA expression profiles across various cancers, constructing benchmark datasets to assess the clinical significance of PRGs in NSCLC. This included evaluating their association with clinical responses and efficacy. Notably, both our and HPA IHC data demonstrated significantly elevated GSDMD‐N protein levels in lung squamous cell carcinoma (LUSC) tissues. Results The expression of PRGs differed significantly between tumor and normal tissues across various cancers, as validated by IHC data, and was correlated with prognosis (p < 0.05). Moreover, our investigation revealed significant differences (p < 0.05) in the expression of the PRGs among distinct TME subtypes categorized as C1 (wound healing), C3 (inflammatory), C2 (IFN‐gamma dominant), C5 (immunological quiet), C4 (lymphocyte deficient), and C6 (TGF‐beta dominant). Additionally, our research on anticancer drug sensitivity uncovered compelling connections between specific anticancer medications and the expression of PRGs, including GSDMD, ELANE, IL18, and CHMP4A (p < 0.05). Conclusion Our study provided valuable insights into the critical role of PRGs in TME modulation, tumor stemness, and anticancer drug sensitivity across diverse cancers. Our findings illuminate the intricate relationship between pyroptosis and the TME, offering new perspectives for enhancing NSCLC treatment and prognosis.

Published in Thoracic Cancer

ISSN: 1759-7706 (Print); 1759-7714 (Online)
Publisher: Wiley
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1759-7714

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