EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

Abstract

Backgrounds It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. Methods The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan–Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. Results In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. Conclusions Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

“…Particularly, the expression and aberrant regulation of HMTs are closely associated with the initiation and progression of lung cancer (36). For instance, EZH2, found to be overexpressed in lung cancer tissues compared to normal lung tissues, is significantly associated with the development and progression of lung cancer (37,38). The level of EZH2 expression correlates positively with the malignancy and poor prognosis in lung cancer (37,38).…”

“…For instance, EZH2, found to be overexpressed in lung cancer tissues compared to normal lung tissues, is significantly associated with the development and progression of lung cancer (37,38). The level of EZH2 expression correlates positively with the malignancy and poor prognosis in lung cancer (37,38). Similarly, EHMT2/G9a is overexpressed in aggressive lung cancer cells and is linked to unfavorable prognosis (39).…”

EZH2 Expression in Head-and-Neck Squamous Cell Cancer in Young Patients

“…Although reviewing all known functions of EZH2 would far exceed the scope of this work, we summarized its main functions associated with tumor cell viability and survival, as shown in Figure 1. EZH2 expression was identified as a negative prognostic marker in multiple solid tumors, including breast, lung, and colorectal cancers [18][19][20] and also HNSCC [21]. malignant cells.…”