Identification and verification of an eight-gene prognostic signature for colorectal cancer based on tumor-associated macrophages.

BACKGROUND: Tumor-associated macrophages (TAMs), a pivotal component of the tumor microenvironment (TME), play an important role in the development and progression of colorectal cancer (CRC). However, the function of macrophage-related genes (MRGs) in CRC remains poorly understood. This research examined the role of MRGs in CRC. METHODS: MRGs were identified by integrating the gene set that exhibited differential expression between tumor and non-tumor tissues in CRC with the gene set associated with TAMs identified by CIBERSORT. To establish a prognostic signature specifically related to TAMs, a combination of univariate Cox regression and least absolute shrinkage operator analyses was utilized. By incorporating oncoPredict, Tumor Immune Dysfunction and Exclusion, mutation, cancer stem cell index, and metastasis data, we were able to predict various clinical features such as drug sensitivity, chemical sensitivity, and immunotherapeutic response. Furthermore, RNA extraction from CRC tissues enabled the validation of differential expression in prognostic MRGs using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: High TAM infiltration was positively associated with poor prognosis, and the macrophage-related gene (MRG) risk score showed a strong correlation with patient survival. The high-risk group demonstrates better immunotherapy response and six of the eight prognostic genes identified were associated with metastasis, suggesting that the high-risk group may be more susceptible to metastasis. The expression levels of two protective genes, MRPS7 and ORC1, were higher in normal tissues compared to tumor tissues. CONCLUSION: Our findings could provide insights into the role of TAMs in predicting CRC prognosis and suggest potential therapeutic targets.