Abstract
BackgroundTumor microenvironment (TME) and tumor-infiltrating immune cells (TICs) greatly participate in the genesis and development of colon cancer (CC). However, there is little research exploring the dynamic modulation of TME.MethodsWe analyzed the proportion of immune/stromal component and TICs in the TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithms. Correlation analysis was conducted to evaluate the association between immune/stromal component in the TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by GO and KEGG enrichment analyses, PPI network, and COX regression analysis. Transforming growth factor β1 (TGFβ1) was finally overlapped from the above analysis. Paired analysis and GSEA were carried out to understand the role of TGFβ1 in colon cancer. The intersection between the difference analysis and correlation analysis was conducted to learn the association between TGFβ1 and TICs.ResultsOur results showed that the immune component in the TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1,110 DEGs obtained from the difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicated that TGFβ1 was significantly associated with the communication of genes in the PPI network and the survival of CC patients. In addition, TGFβ1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in the TGFβ1 up-regulated group were enriched in immune-related activities and the function of TGFβ1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory.ConclusionThe expression of TGFβ1 might be an indicator for the tumor immune microenvironment of CC and serve as a prognostic factor. Drugs targeting TGFβ1 might be a potential immunotherapy for CC patients in the future.
Highlights
Tumor microenvironment (TME) and tumor-infiltrating immune cells (TICs) greatly participate in the genesis and development of colon cancer (CC)
CD8positive (CD8+) tumor-infiltrating lymphocytes (TILs) in the peri-tumoral microenvironment are significantly correlated with poor clinical outcome of salivary gland carcinoma patients (Kesar et al, 2020)
Immune Score was negatively related with M classification of TNM stages (Figure 1D, p = 0.0019)
Summary
Tumor microenvironment (TME) and tumor-infiltrating immune cells (TICs) greatly participate in the genesis and development of colon cancer (CC). Accumulating research has been focusing on understanding the role of the tumor microenvironment (TME) in the genesis and development of cancers. The TME is composed of multiple immune cells, stromal cells, extracellular matrix, and kinds of cytokines and chemokines (Xu et al, 2019). These components in the TME are in a dynamic process, greatly participate in tumor growth, invasion, metastasis, and drug resistance (Li and Wang, 2020; Mikami et al, 2020; Wang S. et al, 2020; Yang et al, 2020). Dual suppression of both PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways in tumor associated macrophages (TAM) could remodel tumor immune microenvironment (TIME) and synergistically activate antitumor immune responses in pancreatic cancer (Li et al, 2020)
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