CSMD1 (CUB And Sushi Multiple Domains 1)

Furthermore, it demonstrated strong predictive performance for genetic mutations, achieving an AUC of 0.99 for CUB and Sushi multiple domains 1 (CSMD1) mutations and 0.86 for Tumor Protein 53 (TP53) mutations in liver cancer. These results highlight the potential of transformer-based weakly supervised learning in computational pathology.

These findings offer new insights into the molecular mechanisms underlying smoking-induced lung carcinogenesis and progression.

We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology.

Consistent with previous research, CSMD1 proved to be one of the most damaging mutations with a significant negative association with vital status. Research indicates a need for further analyses to evaluate prognosis and vital status in melanoma cases and to expand personalized genomic profiling for risk genes across the population.

A multi-omics model combining molecular aberrancies and clinicopathological information was established and proved to be optimal for prognosis prediction of resectable HCC. This model may be helpful for therapeutic strategy selection and survival assessment.

Further validation using TCGA clinical data confirmed PARD6G-AS1 hypomethylation and CD44 overexpression as significant indicators of recurrence (p=0.006 and p=0.02, respectively), and both were linked to advanced stage and lymph node metastasis. The study concludes that PARD6G-AS1 hypomethylation and CD44 overexpression are potential predictors of recurrence in CN-H and CN-L EC patients, respectively.

CellChat analysis highlighted monocytes' central role in immune regulation, with distinct interactions via MIF, galectin, and TGF-β pathways in PCa and BPH. These findings reveal unique immune microenvironments and transcriptional heterogeneity between PCa and BPH, offering potential biomarkers for differentiation and insights into prostate pathology mechanisms.

Spatial-immunophenotyping provided evidence that tumor-cell AXL-upregulation and adverse mutations modulate the tumor microenvironment in favor of infiltrating, activated neutrophils over anti-tumor immune-subsets including CD4 and CD8 T-cells. Tumor-cell AXL-upregulation correlated with distinct oncotypes and microenvironmental immune-profiles that define chemotherapy-induced mechanisms of ICI-resistance, which suggests the combination of AXL inhibitors with current chemoimmunotherapy regimens can benefit NSCLC patients.

Our study has identified CSMD1 as a tumor suppressor in gliomas and elucidated its role in TNF-induced neuroinflammation, contributing to a deeper understanding of glioma pathogenesis.

Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes.

Specifically, hypoxia transcriptionally upregulates the expression of the m6A methyltransferase METTL16 via HIF-1α, and METTL16 directly binds to Lnc-CSMD1-7 and downregulates the RNA stability of Lnc-CSMD1-7 via m6A methylation, ultimately promoting HCC metastasis. Our findings highlight the regulatory function of the METTL16/Lnc-CSMD1-7/RBFOX2 axis in modulating hypoxia-induced HCC progression, which may provide potential prognostic and therapeutic targets for HCC treatment.

To evaluate the effect of FLT3 inhibitors in ALL, we treated ex vivo primary leukemic cells of 6 adult ALL patients (FLT3 mut n=4; FLT3 wt n=2) with increasing concentrations of Gilteritinib, Midostaurin, Crenolanib, Sorafenib and Quizartibin for 24, 48 and 72h. AIRC IG 2019 (Project Code: 23810). Figure 1.