Special issue "The advance of solid tumor research in China": Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling.

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3ß/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment.

Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors.

PURPOSE: Guanylate binding protein 4 (GBP4) is induced by interferons and various cytokines and has been recognized as functionally relevant in numerous types of human cancers. While the role of GBP4 in cancer has been preliminarily summarized, its correlation with antitumor immunity remains unclear and requires further research. METHODS: First, a comprehensive pan-cancer analysis was conducted, focusing on GBP4's expression patterns and immunological functions. Subsequently, we explored the correlations between GBP4 and immunological features within the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) patients. Additionally, we examined the relationships between GBP4 and emerging immunobiomarkers, such as N6-methyladenosine (m6A) genes. Moreover, we assessed the utility of GBP4 in predicting the clinical characteristics and treatment responses of patients with NSCLC. RESULTS: Pan-cancer analysis revealed that GBP4 plays a positive role in most cancer types via the majority of immunomodulators. Furthermore, GBP4 demonstrated positive associations with immunomodulatory factors, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints. Remarkably, the expression of GBP4 was found to be a predictor of significantly enhanced responsiveness to anti-EGFR therapy and immunotherapy. CONCLUSIONS: GBP4 expression profiles offer a promising avenue for identifying highly immunogenic tumors across a wide spectrum of cancers. GBP4 holds potential as a robust pan-cancer biomarker for assessing the immunological characteristics of tumors, with particular relevance to its ability to predict therapeutic responses, notably in the context of anti-EGFR therapy and immunotherapy.