Related Experiment Video
Updated: Sep 21, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
DIRAS2 Is a Prognostic Biomarker and Linked With Immune Infiltrates in Melanoma
Wenli Xue1, Hongbo Zhu2, Hongye Liu1
1Department of Dermatology, The First Hospital of Shanxi Medical University, Tai Yuan City, China.
Background:
Skin cutaneous melanoma (SKCM) is a highly malignant skin tumor. DIRAS2 is considered to be a tumor suppressor gene; however, its function in SKCM has not been explored.
Methods:
The Gene Expression Profiling Interactive Analysis (GEPIA) was implemented to investigate the expression of DIRAS2 in SKCM, and plot the survival curve to determine the effect of DIRAS2 on the survival rates of SKCM patients. Then, the correlation between DIRAS2 and tumor immune infiltration was also discussed, and the expression of DIRAS2 and immune infiltration level in SKCM immune cells was determined using TIMER. The top 100 genes most associated with DIRAS2 expression were used for functional enrichment analysis. In order to confirm the anti-cancer effects of DIRAS2 in SKCM in the data analysis, in vitro assays as well as in vivo studies of DIRAS2 on SKCM tumor cell proliferation, migration, invasion, and metastasis were conducted. Western blot and immunofluorescence assay were employed to study the relationship between DIRAS2 and Wnt/β-catenin signaling pathway in SKCM.
Results:
DIRAS2 expression was shown to be significantly correlated with tumor grade using univariate logistic regression analysis. DIRAS2 was found to be an independent prognostic factor for SKCM in multivariate analysis. Of note, DIRAS2 expression levels were positively correlated with the infiltration levels of B cells, CD4+ T cells, and CD8+ T cells in SKCM. The infiltration of B cells, CD4+ T cells, and CD8+ T cells was positively correlated with the cumulative survival rate of SKCM patients. In vitro experiments suggested that proliferation, migration, invasion, and metastasis of SKCM tumor cells were distinctly enhanced after DIRAS2 knockdown. Furthermore, DIRAS2 depletion promoted melanoma growth and metastasis in vivo. As for the mechanism, silencing DIRAS2 can activate the signal transduction of the Wnt/β-catenin signaling pathway.
Conclusion:
DIRAS2 functions as a tumor suppressor gene in cases of SKCM by inhibiting the Wnt/β-catenin signaling. It is also associated with immune infiltration in SKCM.
