Decreased zinc-fingers and homeoboxes family expression was associated with unfavorable outcomes and immune infiltration in lung adenocarcinoma.

BACKGROUND

The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that play an essential role in developing and progressing diverse malignancies. However, the association of ZHX family expression with prognosis and immune infiltration in lung adenocarcinoma (LUAD) is still unclear. The current study aimed to investigate the relationship between ZHX family expression and clinical outcomes and immune infiltration in LUAD patients.

METHODS

ZHXs family expression was determined by using the Oncomine database and Cancer Cell Line Encyclopedia (CCLE). The impact of ZHXs family expression on prognosis was analyzed by using the Kaplan-Meier-plotter online database. The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to construct the interaction network based on the selected differentially expressed genes associated with ZHXs. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform the enrichment of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The functional state of the ZHXs family in diverse types of malignancies was determined by CancerSEA. The Tumor Immune Estimation Resource (TIMER) database was used to evaluate the association of the ZHXs family with immune cell infiltrates. ZHXs family expression was validated by the Gene Expression Omnibus (GEO) database and real-time polymerase chain reaction (RT-PCR) in 10 paired tumors and normal tissues.

RESULTS

ZHX1-3 expression level significantly decreased in LUAD compared with normal tissues. Attenuated ZHXs expression was significantly associated with unfavorable overall survival in LUAD patients. ZHX family members were positively associated with immune infiltration of monocytes, tumor-associated macrophages (TAMs), M1 and M2 macrophages in LUAD. ZHX family expression was also significantly related to a variety of immune marker sets in LUAD. GEO analysis and RT-PCR validated the significant decrease of ZHXs expression level in LUAD.

CONCLUSIONS

The current study revealed that ZHX family expression was significantly correlated with unfavorable outcomes and immune infiltration in LUAD. The findings herein provide a promising basis for further study into the potential biological function of the ZHX family in LUAD and lay a foundation for developing therapeutic targets for LUAD patients.