AUTHOR=Wang Jie , Akter Rehana , Shahriar Md. Fahim , Uddin Md. Nazim 

TITLE=Cancer-Associated Stromal Fibroblast-Derived Transcriptomes Predict Poor Clinical Outcomes and Immunosuppression in Colon Cancer

JOURNAL=Pathology and Oncology Research

VOLUME=28

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610350

DOI=10.3389/pore.2022.1610350

ISSN=1532-2807

ABSTRACT=<p><bold>Background:</bold> Previous studies revealed that colonic cancer-associated fibroblasts (CAFs) are associated with the modulation of the colon tumor microenvironment (TME). However, identification of key transcriptomes and their correlations with the survival prognosis, immunosuppression, tumor progression, and metastasis in colon cancer remains lacking.</p><p><bold>Methods:</bold> We used the GSE46824, GSE70468, GSE17536, GSE35602, and the cancer genome atlas (TCGA) colon adenocarcinoma (COAD) datasets for this study. We identified the differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, hub genes, and survival-associated genes in colon cancer. Finally, we investigated the correlation of key genes with the survival prognosis, immunosuppression, and metastasis.</p><p><bold>Results:</bold> We identified 246 common DEGs between the GSE46824 and GSE70468 datasets of colonic CAFs, which included 72 upregulated and 174 downregulated genes. The upregulated pathways are mainly involved with cancers and cellular signaling, and downregulated pathways are involved with immune regulation and cellular metabolism. The search tool for the retrieval of interacting genes (STRING)-based analysis identified 15 hub genes and 9 significant clusters in colonic CAFs. The upregulation of <italic>CTHRC1</italic>, <italic>PDGFC</italic>, <italic>PDLIM3</italic>, <italic>NTM</italic>, and <italic>SLC16A3</italic> and downregulation of <italic>FBN2</italic> are correlated with a shorter survival time in colon cancer. The <italic>CTHRC1</italic>, <italic>PDGFC</italic>, <italic>PDLIM3</italic>, and <italic>NTM</italic> genes are positively correlated with the infiltration of tumor-associated macrophages (TAM), macrophages, M2 macrophages, the regulatory T cells (Tregs), T cell exhaustion, and myeloid-derived suppressor cells (MDSCs), indicating the immunosuppressive roles of these transcriptomes in colon cancer. Moreover, the <italic>CTHRC1</italic>, <italic>PDGFC</italic>, <italic>PDLIM3</italic>, <italic>NTM</italic>, and <italic>SLC16A3</italic> genes are gradually increased from normal tissue to the tumor and tumor to the metastatic tumor, and <italic>FBN2</italic> showed the reverse pattern. Furthermore, the <italic>CTHRC1</italic>, <italic>FBN2</italic>, <italic>PDGFC</italic>, <italic>PDLIM3</italic>, and <italic>NTM</italic> genes are positively correlated with the metastatic scores in colon cancer. Then, we revealed that the expression value of <italic>CTHRC1</italic>, <italic>FBN2</italic>, <italic>PDGFC</italic>, <italic>PDLIM3</italic>, <italic>NTM</italic>, and <italic>SLC16A3</italic> showed the diagnostic efficacy in colonic CAFs. Finally, the expression level of <italic>CTHRC1</italic>, <italic>PDGFC</italic>, and <italic>NTM</italic> genes are consistently altered in colon tumor stroma as well as in the higher CAFs-group of TCGA COAD patients.</p><p><bold>Conclusion:</bold> The identified colonic CAFs-derived key genes are positively correlated with survival prognosis, immunosuppression, tumor progression, and metastasis.</p>