Deregulated Methylation and Expression of in Patients with Non-small Cell Lung Cancer: a Novel Prognostic and Immunological Biomarker

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2025 Feb 14

PMID 39949775

Authors

Yue Yuan

Xin Nie

Jiayi Gao

Yumeng Tian

Liuer He

Xue Wang

Ping Zhang

Junling Ma

Lin Li

Affiliations

Soon will be listed here.

Abstract

Backgrounds: Protocadherin gamma subfamily B, 7 (PCDHGB7), a member of the protocadherin family, plays critical roles in neuronal connections and has been implicated in female reproductive system cancers. Its function in lung cancer has not been elucidated.

Methods: We comprehensively investigated PCDHGB7 expression, prognosis, biological function, methylation patterns, and it's relationship with immune infiltration and immunotherapy response through public datasets (HPA, TCGA, GEO, OncoDB and MEXPRESS). Two lung cancer immunotherapy cohorts from our clinical center were enrolled to detect the relationship between methylation and protein levels of in plasma and immunotherapy outcomes.

Results: expression was downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and associated with tumor prognosis. demonstrated a positive correlation with inhibitory immune cells and a negative correlation with tumor mutational burden (TMB) and homologous recombination deficiency (HRD). The methylation level of was upregulated in tumor tissue and negatively correlated with mRNA level. In immunotherapy cohort studies, patients with higher tissue expression showed worse prognosis. Patients with hypermethylation in baseline plasma had shorter progression-free survival (PFS) and overall survival (OS), while those with early reduction of methylation had the best prognosis. Plasma protein levels could predict responses to immune checkpoint inhibitors and function as a prognostic marker for PFS.

Conclusion: expression and methylation are prognostic and immunological biomarkers in non-small cell lung cancer. Plasma methylation and protein levels can be used as novel biomarkers for predicting the efficacy of immunotherapy in lung cancer.

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