SASH3 is an unfavorable prognostic immune biomarker in patients with acute myeloid leukemia(AML).

Abstract

Abstract Background: Acute myeloid leukemia(AML) is a malignant clonal disease. As the most common type of leukaemia, it is characterised by poor treatment outcomes and a poor prognosis in both the paediatric and adult populations. Improving anti-tumour responses through immunomodulators is a promising strategy or a new avenue for AML treatment. Methods: Using publicly available data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we examined the association between SAM And SH3 Domain Containing 3(SASH3) and AML. Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical pathologic features and SASH3. Cox regression and Kaplan-Meier methods were used to determine the clinical characteristics associated with overall survival in patients with AML. Then the relationship between immune infiltration and SASH3 was also analyzed. The research finding was validated by data from the Gene Expression Omnibus (GEO) database. Results: Compared to normal patients, SASH3 expression in AML patients was significantly higher (p = 3.05e-34) and strongly associated with survival. In addition, SASH3 expression was significantly correlated with survival outcome (p = 5.3E-03) and cytogenetic risk (p = 3E-04) in AML. SASH3 expression was correlated with the expression of the genes HCK, SYK, FYN, ITGB2, PIK3CD, FGR, PIK3R5, VAV1, LCP2, and GRB2. Our study suggests that SASH3 expression is strongly associated with AML development and survival outcomes as well as multiple cancer-related genes and pathways, such as the HCK(Hematopoietic cell kinase) and regulation of small GTPase-mediated signal transduction. Conclusion: Our study revealed that SASH3 expression is closely associated with AML development and survival outcome, as well as multiple cancer-related genes and pathways, thus highlighting SASH3 as a potential therapeutic marker of AML.