Considering that CAFs are mainly transformed by fibroblasts under the stimulation of growth factors and that normal fibroblasts can also acquire the phenotype of CAFs by communicating with cancer cells, early CAFs exhibit similar functions as normal fibroblasts; The “TNF signaling pathway” and “IL-17 signaling pathway” are the most important pathways, which are significantly enriched in CAFs in middle developmental stages (cluster 2), and TNF (tumor necrosis factor) serves as the role of immunomodulator [29]. This evidence concerns the gene TNF and cancer.