ERBB3 mediates the PI3K/AKT/mTOR pathway to alter the epithelial‑mesenchymal transition in cervical cancer and predict immunity filtration outcome.

Abstract

Cervical cancer is the fourth most common cancer among women worldwide, and the prognosis of advanced/recurrent cervical cancer remains poor. Metastasis and invasion of this type of cancer are closely associated with the tumor microenvironment. Studying the complex interactions between tumor progression and immune cells or stromal cells can provide new insights into treatment for patients with aggressive tumor, recurrence and drug resistance. In the present study, a bioinformatics method (Gene Expression Profiling Interactive Analysis, differentially expressed genes, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interactions and survival analysis) was used to explore the mRNA and protein level discrepancy gene signature of ERBB3 via the PI3K/AKT/mTOR pathway from the speculation in immuno-oncology and experimental verification of different cervical cancer cell lines. The high expression of ERBB3 in cervical cancer tissues (especially HPV-positive and adenocarcinoma-related) promoted the activation of the PI3K/AKT/mTOR pathway. The increased expression of MMP9 changed the macrophage infiltration in the tumor microenvironment and affected prognosis of patients with cervical cancer. In conclusion, the present study identified 14 EMT-related genes and 30 genes involved in the PI3K/AKT/mTOR pathway in cervical cancer, and they might provide novel clues for future treatment. The MMP family may be a notable factor associated with tumor cells and immune cells.