Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 207 - 207

Published: March 18, 2025

Background: The reprogramming of lipid metabolism, especially glycerolipid metabolism (GLM), plays a key role in cancer progression and response to therapy. However, the molecular characterization GLM pancreatic (PC) remain unclear. Methods: A pan-cancer analysis metabolism-related genes (GMRGs) was first conducted assess copy-number variants, single-nucleotide variations, methylation, mRNA expression. Subsequently, PC characterized using lipidomics, single-cell RNA sequencing (scRNA-seq), spatial transcriptomic analysis. cluster based on bulk data from 930 samples identified GLM-associated subtypes, which were then analyzed for differences prognosis, biological function, immune microenvironment, drug sensitivity. To prioritize prognostically relevant GMRGs PC, we employed random forest (RF) algorithm rank their importance across samples. Finally, biomarker validated PCR immunohistochemistry. Results: Pan-cancer features cancers, while scRNA-seq, transcriptomics, lipidomics highlighted heterogeneity PC. Two subtypes with significant prognostic, biofunctional, microenvironmental, sensitivity ALDH2 as novel prognostic large number datasets clinical Conclusions: This study highlights crucial defines new subtype biomarker. These findings establish avenue studying prediction precision medicine patients.

Language: Английский

---

Integrative Analysis of Transcriptomic Data Reveals a Predictive Gene Signature for Chemoradiotherapy Response in Rectal Cancer

Published: Jan. 1, 2025

BackgroundLocally advanced rectal cancer (LARC) is treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery, achieving pathological complete response (pCR) in ~15% of cases. Enhancing pCR through combined nCRT and chemotherapy increases toxicity, while many patients fail to benefit from nCRT, experiencing significant side effects. Predicting could enable non-surgical management via a watch-and-wait strategy spare non-responders unnecessary toxicity. However, no gene expression signatures predicting have yet been clinically implemented.MethodsWe conducted differential analysis across six GEO datasets integrated four microarray refine findings. Using machine learning, we developed signature predictive validated it cross-validation. Gene set enrichment (GSEA) identified biological pathways linked response. Spatial transcriptomic profiling using GeoMx Digital Profiling (DSP) technology was performed on pre-treatment biopsies uncover compartment-specific markers within tumor stroma.ResultsThe achieved strong performance (AUC = 0.80) GLMnet Random Forest models significantly associated consensus molecular subtypes (CMS4) immune (iCMS3). GSEA revealed related VEGFR, EGFR, Toll-like receptor signaling. transcriptomics eight genes, tumor-associated genes showing higher value than stroma-associated markers.ConclusionWe present novel LARC potential guide personalized treatment. highlights the microenvironment's contribution therapy outcomes, warranting further validation larger cohorts.

Language: Английский

---

Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

Cancer Innovation, Journal Year: 2024, Volume and Issue: 4(1)

Published: Dec. 5, 2024

Abstract Background The incidence of alcohol‐associated cancers is higher within Asian populations having an increased prevalence inactivating mutation in aldehyde dehydrogenase 2 ( ALDH2 ), a mitochondrial enzyme required for the clearance acetaldehyde, cytotoxic metabolite ethanol. role alcohol consumption promoting lung cancer controversial, and little attention has been paid to association between drinking pulmonary expression. Methods We performed comprehensive bioinformatic analysis multi‐omics data available public databases elucidate adenocarcinoma (LUAD). Results Transcriptional proteomic indicate substantial expression ALDH2, which functional metabolism diffused from bronchial circulation. healthy tissue than LUAD inhibits cell cycle, apoptosis, epithelial–mesenchymal transition pathways. Moreover, low mRNA levels predict poor prognosis overall survival patients. Interestingly, correlates with immune infiltration LUAD. Conclusions A better understanding tumor progression might support its potential use as prognostic marker therapeutic target improving immunotherapeutic response.

Language: Английский

---

Multi-omics data integration reveals novel genes related to autoimmune hypothyroidism in the brain: A molecular basis for the brain–thyroid axis

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 136, P. 111239 - 111239

Published: Dec. 28, 2024

Language: Английский

---