Identification of an M1 Macrophages-Related Signature for Predicting the Survival and Therapeutic Response in Gastric Cancer.

This research aimed to determine genes associated with M1 TAMs (tumour-associated macrophages) and to develop an M1 TAMs-related signature for predicting GC (Gastric cancer)'s prognosis and therapeutic effect. Based on the GC dataset in TCGA, we constructed a prognostic signature using M1 TAMs-related genes and validated it using data from the GEO dataset. To evaluate the predictive power of the signature, the survival curves, ROC curves, Cox regression analysis, nomograms and calibration curves were constructed. Differences in immune infiltration, immunotherapy response, and chemotherapy sensitivity between the two risk groups were also analysed. Furthermore, by jointly using the string database and Cytoscape software, we identified the hub gene that differed between the two risk groups. In the end, the expression and function of the identified hub gene were validated using fresh tissue specimens and GC cell lines. A six-gene risk signature was developed based on M1 TAMs-related genes. Furthermore, the ROC curve, nomogram, calibration plot of the nomogram and Cox regression analysis confirmed M1 TAMs co-expressed genes have a strong predictive performance of the six-gene risk signature. Immune infiltration analysis and the TIDE algorithm indicated that low-risk GC patients may be more suitable for immunotherapy. Finally, fibronectin 1 (FN1), the hub gene with the highest degree of interaction between high- and low-risk groups, indicated a significant correlation with survival differences in GC. Functional analysis demonstrated that FN1 promotes GC cell proliferation, invasion, migration and EMT. The risk signature of six M1 TAMs co-expressed genes can be used to evaluate the prognosis and treatment efficacy of patients with GC, providing a basis for selecting new therapies for patients. The FN1 gene is the hub gene with predictive value in this signature, and it is upregulated in GC and functions as an oncogene.