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Background  Tumor-associated macrophages are important components of the tumor microenvironment, and the macrophage phenotypic switch has been shown to correlate with tumor development. However, the use of a macrophage phenotypic switch-related gene (MRG)-based prognosis signature for lung adenocarcinoma (LADC) has not yet been investigated.    Methods  In total, 1,114 LADC cases from two different databases were collected. The samples from TCGA were used as the training set (N = 490), whereas two independent datasets (GSE31210 and GSE72094) from the GEO database were used as the validation sets (N = 624). A robust MRG signature that predicted clinical outcomes of LADC patients was identified through multivariate COX and Lasso regression analysis. Gene set enrichment analysis was applied to analyze molecular pathways associated with the MRG signature. Moreover, the fractions of 22 immune cells were estimated using CIBERSORT algorithm.    Results  An eight MRG-based signature comprising CTSL, ECT2, HCFC2, HNRNPK, LRIG1, OSBPL5, P4HA1, and TUBA4A was used to estimate the LADC patients’ overall survival. The MRG model was capable of distinguishing high-risk patients from low-risk patients and accurately predict survival in both the training and validation cohorts. Subsequently, the eight MRG-based signature and other features were used to construct a nomogram to better predict the survival of LADC patients. Calibration plots and decision curve analysis exhibited good consistency between the nomogram predictions and actual observation. ROC curves displayed that the signature had good robustness to predict LADC patients’ prognostic outcome.    Conclusions  We identified a phenotypic switch-related signature for predicting the survival of patients with LADC.

Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma