Sapitinib

We focused on the FOXN3 gene and selected its antisense transcripts (FOXN3-AS1) to investigate its potential involvement in acute myeloid leukemia (AML).

Several integrated multi-omics datasets have expanded the horizons of the cancer landscape. With the emergence of new high-throughput technologies, a large number of non-coding RNAs have been confirmed to be involved in the pathogenesis of different types of hematological malignancies.

We conducted experimental validation using quantitative polymerase chain reaction (qPCR) with bone marrow specimens from AML patients. Then, Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves were used to substantiate the prognostic association between FOXN3-AS1 and AML patients within the TCGA database. Correlation between FOXN3-AS1 expression and gene mutation, immune, and immune function using Spearman correlation analysis. To explore the physical and functional interaction between FOXN3-AS1 and the DNMT1 protein, we utilized the RPISeq web tool from Iowa State University. Subsequently, we performed qPCR experiments to test the effect of 5AzaC (DNMT1 inhibitor) on FOXN3-AS1 expression AML cell lines (THP1 and OCI-AML3). We leveraged the “OncoPredict” R package in conjunction with the Genomics of Drug Sensitivity (GDSC) database to predict drug response in AML patients expressing FOXN3-AS1.

We observed a significant upregulation of FOXN3-AS1 expression in AML patients compared to healthy controls using clinical samples. The TCGA database revealed an association between high FOXN3-AS1 expression and adverse prognosis. In our subsequent analysis, genes with poor prognostic implications in AML patients were exclusively identified in the FOXN3-AS1 high-expression group, further corroborating this relationship. AML patients with higher FOXN3-AS1 expression levels may respond less optimally to immunotherapy than patients with lower levels. Besides, we computationally predicted the interaction of FOXN3- AS1 and DNMT1 protein and experimentally confirmed that DNMT1i (GSK-3484862) affects the expression level of FOXN3-AS1. We also found that the chemotherapy drugs (5-Fluorouralic, Cisplatin, Dactolisib, Sapitinib, Temozolomide, Ulixertinib, Vinorelbine, Ruxolitinib, Osimertinib and Cisplatin) showed favorable responses in AML patients with high FOXN3-AS1 expression levels.

Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML.

Oral cancer is an aggressive malignancy with a survival rate below 50% in advanced stages due to low mutation rates, lack of molecular subtypes, and limited treatment targets. This study presents a pioneering approach to classifying oral cancer subtypes based on the morphology of patient-derived organoids (PDOs) and proposes a therapeutic strategy. We establish 76 cancer and 81 normal PDOs. For cancer PDOs, both manual classification and AI-based scoring are utilized to categorize them into three distinct subtypes: normal-like, dense, and grape-like. These subtypes correlate with unique transcriptomic profiles, genetic mutations, and clinical outcomes, with patients harboring dense and grape-like organoids exhibiting poorer prognoses. Furthermore, drug response assessments of 14 single agents and cisplatin combination therapies identify a synergistic treatment approach for resistant subtypes. This study highlights the potential of integrating morphology-based classification with genomic and transcriptomic analyses to refine oral cancer subtyping and develop effective treatment strategies.