Novel fatty acid metabolism biomarkers of immunotherapy response in cervical cancer

Abstract

Fatty acid metabolism abnormalities played an important role in cervical cancer, and current tumor stage has entered the molecular era, which determined the genomic characteristics and prognosis of cancer more precisely than the traditional TNM stage. However, molecular typing on cervical cancer based on fatty acid metabolism has not yet been unclear. Here we downloaded the gene set of fatty acid metabolism from the MSigDB database and classified cervical cancer into three independent genomic stage types-C1, C2 and C3, by extracting the expression in TCGA. Kaplan-Meier survival analysis showed significant survival differences among the three (p < 0.05), and MCPcounter analysis showed that CD8+ T-cell infiltration was more in C3, which had the best prognosis. The MCPcounter analysis showed more CD8+ T-cell infiltration in the C3 type with the best prognosis and more fibroblast infiltration in the C1 type with the worst prognosis (p < 0.05). WGCNA analysis was performed on the three molecular typologies to identify the best correlated blue modules, identify the co-expressed genes in which the association was greater than 0.3, and take the intersection with the differential genes of the three molecular typologies. A novel prognostic model for fatty acid metabolism genomics was developed. Survival analysis showed better survival differences in this model with higher immune and stromal scores in the low-risk group. 31 genes in the model were negatively correlated with immune checkpoints overall. For immunotherapy efficacy analysis, the immunotherapy efficacy was higher in the low-risk group than in the high-risk group in IPS score, and the immune dysfunction level was higher in the low-risk group than in the high-risk group in the TIDE algorithm, whereas the immune escape ability was higher in the high-risk group than in the low-risk group, and the immunotherapy level was higher in the high-risk group than in the low-risk group overall (p < 0.05). Mechanistically, the high-risk group was mainly enriched in the pathways of intercellular interaction, cell-matrix remodeling, angiogenesis, and epithelial-mesenchymal transition. In conclusion, the prognostic model of cervical cancer constructed based on the molecular typing of fatty acids metabolism could predict the prognosis and immunotherapy of the patients with cervical cancer.