The overall survival of metastatic
colon adenocarcinoma (
COAD) remains poor, so it is important to explore the mechanisms of
metastasis and invasion. This study aimed to identify invasion-related
genetic markers for prognosis prediction in patients with
COAD. Three molecular subtypes (C1, C2, and C3) were obtained based on 97
metastasis-related genes in 365
COAD samples from The
Cancer Genome Atlas (TCGA). A total of 983 differentially expressed genes (DEGs) were identified among the different subtypes by using the limma package. A 6-gene signature (ITLN1, HOXD9, TSPAN11, GPRC5B, TIMP1, and CXCL13) was constructed via Lasso-Cox analysis. The signature showed strong robustness and could be used in the training, testing, and external validation (GSE17537) cohorts with stable predictive efficiency. Compared with other published signatures, our model showed better performance in predicting outcomes. Pan-
cancer expression analysis results showed that ITLN1, TSPAN11, CXCL13, and GPRC5B were downregulated and TIMP1 was upregulated in most
tumor samples, including
COAD, which was consistent with the results of the TCGA and GEO cohorts. Western blot analysis and immunohistochemistry were performed to validate
protein expression.
Tumor immune infiltration analysis results showed that TSPAN11, GPRC5B, TIMP1, and CXCL13
protein levels were significantly positively correlated with CD4+ T cells, macrophages, neutrophils, and dendritic cells. Further, the TIMP1 and CXCL13
proteins were significantly related to the
tumor immune infiltration of CD8+ T cells. We recommend using our signature as a molecular prognostic classifier to assess the prognostic risk of patients with
COAD.