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Baseline cellular state shapes the molecular impact of mutant KRAS alleles in reconstituted pancreatic cancer cells
Mol Omics. 2026 Sep 10:aaiag022. doi: 10.1093/molecular-omics/aaiag022. Online ahead of print.
ABSTRACT
KRAS is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumor initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signaling programs in PDAC cells remains unresolved. Here, we systematically interrogated the molecular consequences of seven common KRAS mutant variants in reconstituted isogenic, KRAS-deficient PDAC cell lines by integrated transcriptomic, proteomic, and phosphoproteomic profiling. We found that baseline cellular state, rather than allele identity, was the predominant driver of molecular variation. Comparisons with established KRAS reference signatures revealed significant but moderate overlap at the mRNA level and less so at the proteome level. Pathway analyses highlighted interferon response and mitochondrial translation-related proteins as recurrently altered across mutant alleles, while phosphoproteomic data confirmed robust ERK1/2 activity and suppression of DYRK kinase substrates by mutant KRAS expression. Importantly, no robust mutant allele-specific molecular programs were identified in our KRAS-reconstituted cell lines. Together, our study establishes a comprehensive multi-omics resource for KRAS signaling in PDAC and demonstrates that cellular context exerts a stronger influence than allele identity in shaping molecular profiles, with implications for interpreting putative allele-specific signaling dependencies.
PMID:42720273 | DOI:10.1093/molecular-omics/aaiag022
Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic review
npj Digital Medicine, Published online: 10 September 2026; doi:10.1038/s41746-026-03228-7
Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic reviewTargeting the MNK1-MYH9 axis blocks YAP1 recruitment to prevent thrombosis and platelet activation-induced NETosis
PACE: Perceived-Latency-Aware Cascading Service Routing and Filler Control for QoE-Efficient Retrieval-Augmented Dialogue Serving
Visualizing the Invisible: Generative Visual Grounding Empowers Universal EEG Understanding in MLLMs
SHP1 expression in tumor-associated dendritic cells drives immunoevasion via impairing CD8<sup>+</sup> memory T cell responses
Oncogenesis, Published online: 15 May 2026; doi:10.1038/s41389-026-00627-z
SHP1 expression in tumor-associated dendritic cells drives immunoevasion via impairing CD8+ memory T cell responsesBaseline cellular state dictates the molecular impact of KRAS mutant variants in pancreatic cancer cells
bioRxiv [Preprint]. 2026 Mar 12:2026.03.10.710185. doi: 10.64898/2026.03.10.710185.
ABSTRACT
KRAS is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumor initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signaling programs in PDAC cells remains unresolved. Here, we systematically interrogated the molecular consequences of seven common KRAS mutant variants in reconstituted isogenic, KRAS-deficient PDAC cell lines by integrated transcriptomic, proteomic, and phosphoproteomic profiling. We found that baseline cellular state, rather than allele identity, was the predominant driver of molecular variation. Comparisons with established KRAS reference signatures revealed significant but moderate overlap at the mRNA level and less so at the proteome level. Pathway analyses highlighted interferon response and mitochondrial translation as recurrently altered across alleles, while phosphoproteomic data confirmed robust ERK1/2 activity and suppression of DYRK kinase substrates by mutant KRAS expression. Importantly, no robust allele-specific molecular programs were identified. Together, our study establishes a comprehensive multi-omics resource for KRAS signaling in PDAC and demonstrates that cellular context exerts a stronger influence than allele identity in shaping molecular profiles, with implications for interpreting putative allele-specific signaling dependencies and therapeutic vulnerabilities.
PMID:41959224 | PMC:PMC13060958 | DOI:10.64898/2026.03.10.710185
Unifying Group-Relative and Self-Distillation Policy Optimization via Sample Routing
Correction: Integrative multi-omics and machine learning reveals the spatial niche distribution and role of CYP27A1+TAMs in immunotherapy response in non-small cell lung cancer
Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.
ABSTRACT
[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].
PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612
Correction: Integrative multi-omics and machine learning reveals the spatial niche distribution and role of CYP27A1+TAMs in immunotherapy response in non-small cell lung cancer
Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.
ABSTRACT
[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].
PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612
Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model
Route-Induced Density and Stability (RIDE): Controlled Intervention and Mechanism Analysis of Routing-Style Meta Prompts on LLM Internal States
SortedRL: Accelerating RL Training for LLMs through Online Length-Aware Scheduling
Cerebra: A Multidisciplinary AI Board for Multimodal Dementia Characterization and Risk Assessment
Do Vision-Language Models Measure Up? Benchmarking Visual Measurement Reading with MeasureBench
Non-classic deubiquitinase USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A
Oncogene, Published online: 24 March 2026; doi:10.1038/s41388-026-03730-y
Non-classic deubiquitinase USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3AIntegrated Machine Learning and Multi-Omics Identifies a Novel Molecular Signature for Improving the Prognosis of Hepatocellular Carcinoma
J Hepatocell Carcinoma. 2026 Mar 11;13:574690. doi: 10.2147/JHC.S574690. eCollection 2026.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) exhibits significant molecular heterogeneity and complex immune microenvironment, which to some extent limits the accuracy of prognosis assessment and the formulation of individualized treatment strategies. This study aims to identify immune-derived molecular signatures based on multi-omics data and machine learning methods for the prognosis prediction and risk stratification of HCC.
METHODS: Based on weighted gene co-expression network analysis(WGCNA) and differential gene analysis,immune-derived molecular signature (IDMS) were screened in both single-cell and bulk transcriptomes. Prognostic model was constructed by multi-machine learning approachs. Subsequently, we investigated the differences in mutations, biological functions, and immune cell infiltration within the tumor microenvironment between the high- and low-risk groups.In addition, we comprehensively analyzed the drug sensitivity of IDMS and predicted potential drugs.
RESULTS: We identified seven hub genes at the single-cell and bulk transcriptome levels. Based on multiple machine learning, we constructed a prognostic model that demonstrated excellent performance in predicting overall survival for patients with HCC. IDMS -integrated normograms provide a promising and quantitative tool for clinical risk management.Notably, a significant difference in microsatellite instability (MSI) was observed between the high- and low-risk groups. This indicates that patients in the high-risk group might have a better response to immunotherapy. Additionally, we predicted potential drugs targeting to these risk subgroups.
CONCLUSION: Our research developed an IDMS that could serve as an effective tool for patient stratification management and prognosis prediction. This signature could provide a reference for immunotherapy for patients with HCC and improve their prognosis.
PMID:41847219 | PMC:PMC12991065 | DOI:10.2147/JHC.S574690
MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
Cell Death Discovery, Published online: 11 March 2026; doi:10.1038/s41420-026-02990-7
MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism