Identification of driver genes regulating immune cell infiltration in cervical cancer by multiple omics integration

Abstract

Cervical cancer (CC) is one of the most common cancers in women. However, copy number alteration (CNA)-driven dysregulated genes and their functions in CC are still rarely investigated. In the present study, we conducted integrative analysis of CNA and gene expression data from The Cancer Genome Atlas (TCGA) cervical cancer to identify dysregulated genes triggered by CNAs. The integration of copy number status and RNA expression revealed 763 amplified and 1,391 deleted genes significantly dysregulated by the CNAs (P-value < 1e-8). Among these CNA genes, five driver genes, including PI3KCA, PI3KCB, DVL3, WWTR1, and ERBB2, exhibited a strong association with immune cell infiltration, suggesting that the pathways that they participate in may be involved in regulating immune cell infiltration. Moreover, we also observed that the genes of immunotherapeutic targets were abundantly expressed in the wild-type samples, suggesting that immunotherapy based on these immunotherapeutic targets may be applied to wild-type samples. In addition, the two CNA driver genes, DVL3 and ERBB2, might be sensitive and resistant biomarkers for examining the tumor’s response to chemoradiotherapy, respectively. Particularly, the expression of ERBB2 was also observed to be higher in responders of chemotherapy than non-responders. Furthermore, a subset of CNA genes was identified to predict the prognosis of cervical cancer. In summary, our systematic data analysis of these CNA genes not only improved our understanding of the veiled mechanism behind immune cell infiltration, but also provided the potential clinical application of these CNA genes in cervical cancer.