Identification of Key Pathways and Establishment of a Seven-Gene Prognostic Signature in Cervical Cancer

Abstract

Cervical cancer (CC) remains high morbidity and mortality. We aimed to identify critical pathways underlying cervical carcinogenesis and establish a prognostic signature. Six datasets from the gene expression omnibus (GEO) database were used to screen the differentially expressed genes (DEGs) between CC and normal tissues. We used the unions of the DEGs to perform functional analysis. The 108 overlapped DEGs were analyzed to determine a prognostic signature by Cox regression and Lasso analysis based on The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) and Immune Cell Abundance Identifier (ImmuCellAI) were used to determine the relationships between the signature and biological functions. The PI3K-Akt signaling pathway, the Ras signaling pathway, and the viral carcinogenesis pathway may be critical for CC development. We identified seven genes (PLOD2, DSG2, SPP1, CXCL8, MCM5, HLTF, and KLF4) to construct a risk score formula. Survival analysis showed that the high-risk group indicated a worse prognosis than the low-risk group $\left(p<0.0001\right)$ . The AUC of the prognostic signature was 0.7449, 0.7641, and 0.8146 at 1, 3, and 5 years. We also identified that the signature is an independent prognostic factor. GSEA showed five pathways were relevant to the signature, such as the adherens junction pathway. The signature also affected the abundances of various types of immune cells, such as B cell, CD4+ T cell, and CD8+ T cell. Further, we found that SPP1 was co-expressed with HK3, CD163, CCL3, CLEC5A, MMP8, TREM1, OLR1, and TREM2. The results of Gene Ontology analysis showed that SPP1 and its co-expressed related proteins mainly affected metabolic process, multicellular organismal process, cell communication, cell proliferation, protein binding, and transporter activity. In conclusion, the present study explored the key pathways for CC development and the seven-gene signature can effectively make the prognosis evaluation of CC patients.