HOXC6/8/10/13 predict poor prognosis and associate with immune infiltrations in glioblastoma.

Background: Glioblastoma (GBM), characterized by deregulated cell proliferation and immune cells infiltration, is a common and lethal tumor of the central nervous system. Recently, the infiltration of immune cells has attracted attention as a potential novel GBM immunotherapy option. Homeobox C cluster (HOXC) is an evolutionarily conserved family of transcriptional factors that are involved in embryogenesis and tumorigenesis. Nevertheless, the correlations of HOXCs with the prognosis and immune infiltration of GBM remain blurred.

Methods: The RNA-seq data with corresponding clinical characteristics were downloaded from TCGA and GTEx databases. The correlations between HOXCs and clinical characteristics were calculated using univariable and multivariate Cox regression. R language with ggplot2, survminer, survival, GSVA, and pROC packages were employed to analyze the data and present the plots. MethSurv, UALCAN and cBioPortal were employed to evaluate the DNA methylation and mutation status of HOXCs in GBM. We also verified the expression and prognosis of HOXCs by qPCR and immunohistochemistry in a cohort of 36 patients.

Results: We identified that HOXC6/8/10/13 were crucial biomarkers for diagnosis and prognostic judgement in GBM. Gene set variation analysis revealed that levels of expression of HOXCs were associated with the infiltration of various immune cells. The qPCR and immunohistochemistry data validated the prognostic values of HOXC6/8/10/13 in GBM. Finally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that HOXCs might be involved in DNA-binding transcription activator activity and the apelin signaling pathway.

Conclusion: This research highlights that HOXC6/8/10/13 are involved in the immune infiltrates, also provide potential clinical utility as therapeutic targets in GBM.