Systemic Profiling of KDM5 Subfamily Signature in Non-Small-Cell Lung Cancer

Despite improvements in diagnosis and treatment, lung cancer is one of the most lethal human diseases, with a dismal 5-year relative survival rate of only 5% for patients diagnosed with advanced metastatic disease. Accumulating evidence supports that epigenetic aberration of histone demethylase-KDM5 subfamily is linked to human pan-cancer. However, the detailed functions of KDM5 proteins in lung cancer, especially in non-small-cell lung cancer (NSCLC), remain poorly understand.

UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal, TIMER, TISIDB, and STRING databases were utilized in this investigation.

We detected varying degrees of gene mutations of KDM5 subfamily members and found that KDM5B/C were remarkably overexpressed in LUAD and LUSC compared to normal tissues. Different from KDM5D, positive relationship was shown between overall survival and mRNA expression of KDM5A/B/C in lung cancer. We determined that KDM5A/B/C expression levels were positively correlated with CD4+ T cells infiltration, especially immunological markers of Tregs and Th17 cells. Moreover, LUAD and LUSC were separately rich in inflammatory and wound healing subtypes after immunogenomics analyzing with respect to KDM5 subfamily overexpression. And with their 120 co-expressed genes, we revealed that nucleocytoplasmic transport and cellular protein localization-related genes were closely connected to KDM5 subfamily alterations, next to chromatin remodeling genes.

We formulated the immune-infiltrating and prognostic value of KDM5 subfamily and highlighted its promising role in immune-inflammatory interaction with tumour microenvironment in NSCLC.