Transcriptional profiling of the tumor microenvironment of recurrent and non-recurrent stage II colon cancer

Predicting recurrences in patients with stage II colon cancer remains a clinical challenge. This study aimed to uncover connections between gene expression, clinicopathological characteristics, and recurrence in patients with stage II colon cancer. Gene expression profiling was conducted on primary tumors from 94 well-characterized patients with stage II colon cancer using the PanCancer IO 360™ panel from NanoString Technologies, which includes 770 mRNAs related to tumor progression and the tumor microenvironment. Unsupervised hierarchical clustering, differential gene expression (DEG) and survival analyses were used to describe the relationship between gene expression, clinicopathological characteristics, and recurrence. Unsupervised hierarchical clustering revealed distinct gene expression patterns in pT4 tumors, particularly in pathways involving immune cell localization and myeloid cell activity. DEG analysis identified 156 differentially expressed genes in pT4 versus pT3 tumors, including the important chemokines, CCL2 and CXCL8, and the cytokine LIF. In addition, 35 upregulated genes associated with migration and extracellular processes were identified in patients with recurrence. Finally, SLC2A1 and VEGFA emerged as independent prognostic markers for time to recurrence and overall survival. In conclusion, this study unveiled distinct gene expression patterns in advanced pT4 tumors, and identified independent prognostic biomarkers that may prove useful in stage II colon cancer.