Prognostic significance and immunologic features of the paired-box (PAXs) family: a pan-cancer multi- omics analysis

Abstract

Abstract Objective The PAX genes, comprising a family of nine clearly defined paired-box transcription factors, are associated with the onset and progression of certain tumors. Even so, no extensive systematic investigation toward the contribution of PAX genes in pan-cancer has been implemented. Methods The development and modulation of the PAX gene family in pan tumor and its correlations with prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), immunological subtypes, immune checkpoint genes, tumour stemness, tumor microenvironment, chemotherapeutics sensitivity, and effectiveness of immunotherapy were explored by bioinformatics analysis, based on multi-omics data from TCGA, GEO, cBioPortal, and TIMER database. Results We observed the significant correlations between the regulation of particular PAX family members in pan tumor and the survival prognosis and tumor stage of patients, TMB, MSI, stemness scores, immune cells infiltration, etc. The PAX gene family exhibited some degree of heterogeneity in different cancers in terms of the above mentioned findings. It has also been revealed in the present multiple omics study that the expression for most of the PAX family members, including PAX1/3/5/8/9, is significantly correlated with copy number variation. Moreover, we also found that several PAX family members were clearly associated with expression of immune checkpoint genes, the sensitivity to chemotherapy agents, and anti-PD-L1/PD-1 immunotherapy. Furthermore, the invading immune evaluation in bladder tumors displayed substantial correlations between PAX gene variations in copy number or substitution levels and the extent of multiple immune cell infiltration. In addition, the mRNA and amino acid manifestations of PAX8 in BLCA were validated using real-time PCR (RT-PCR) and the Human Protein Atlas (HPA). Conclusion In summary, our findings highlight the importance of PAX family genes in predictions of various tumor types, as evidenced by multiple datasets and identified PAX-associated genes that could be used as targets for therapies. These results suggest that PAX family related genes can be used as potential prognostic markers for cancer. It represents a systematic analysis of the further function of PAX family genes, which can provide new ideas for the prognosis and treatment of various cancers.