Search bioRxiv⌕ Search

Biology subjects

Alanany, R.

Publications and source records attributed to Alanany, R..

2 recordsLinked to original sources
bioRxiv2026

Methylation-Guided Stratification of Colorectal Cancer Reveals Immune Subtypes with Distinct Clinical Outcomes

BackgroundAberrant DNA methylation is a hallmark of colorectal cancer (CRC). Yet, how DNA methylation is linked to transcriptional states, immune programs, and tissue resident microbiome within the same tumors has not been systematically analyzed. MethodsWe profiled genome-wide DNA methylation (Illumina MethylationEPIC) in 182 colon tumors and 76 adjacent normals from AC-ICAM, and integrated with matched transcriptomes, whole exome, microbiome, and clinical data. Tumor-specific methylation, promoter methylation-expression links, microbiome associations, and survival were analyzed and validated in TCGA-COAD. ResultsTumor and normal tissues exhibited distinct DNA methylation patterns, reflecting widespread epigenetic alterations in cancer. Pathway analysis identified two major tumor pathways regulated by DNA methylation. The first involved extracellular signaling and adhesion genes, with higher methylation linked to increased proliferation and lower immune infiltration. Similarly, higher tumor methylation in nitric oxide signaling was associated with reduced adaptive immune activity and interestingly, influenced immune-related survival. These findings were also validated in the TCGA-COAD cohort. An inverse methylation-expression pattern implicated modifications of TCR signaling in naive CD8, and interferon-/{beta} signaling which were hypermethylated and hypomethylated in tumors compared to normal, respectively. Combining methylation and microbiome revealed connections between Akkermansia muciniphila and TGF-{beta} and Prevotella nigrescens with MAPK signaling pathways. Finally, a methylation-based model using 43 promoters CpGs successfully identified patients with different survival outcomes, underscoring the clinical relevance of these epigenetic alterations in colon cancer. ConclusionDNA methylation shapes the molecular and immune landscape of colon cancer, altering signaling pathways and immune programs, interacting with the microbiome, and impacting patients survival.

cancer biology↗
bioRxiv2025

SLFN11 Enhances Cisplatin Sensitivity in Pediatric Cancer via Activation of Stress-Response and Suppression of Survival Pathways

Pediatric cancers pose significant treatment challenges due to their biological heterogeneity and variable responses to chemotherapy. SLFN11, a DNA/RNA helicase-like protein known to sensitize adult tumors to DNA-damaging agents, remains underexplored in pediatric malignancies. Here, we investigate the role of SLFN11 across pediatric Wilms tumor, osteosarcoma, and medulloblastoma using integrated bioinformatics, epigenetic profiling, and functional assays. In silico analysis of TARGET and ICGC datasets revealed distinct correlations between SLFN11 expression and patient survival, with positive, negative, or neutral predictive value depending on tumor type. Baseline expression and promoter methylation analysis in pediatric cancer cell lines demonstrated epigenetic regulation of SLFN11, similar to adult cancers. Using CRISPR-dCas9-mediated activation, we successfully upregulated SLFN11, which significantly enhanced sensitivity to cisplatin and the PARP inhibitor talazoparib across all tested cell lines. Transcriptomic profiling under cisplatin treatment indicated that SLFN11 modulates DNA damage response and MAPK signaling pathways, potentially contributing to chemotherapy sensitivity. These findings establish SLFN11 as a context-dependent predictive biomarker and a potential therapeutic target to overcome chemoresistance in pediatric solid cancers.

cancer biology↗