bioRxiv [Preprint]. 2025 Aug 25:2025.08.21.671519. doi: 10.1101/2025.08.21.671519.

ABSTRACT

Lung cancer is the most common cause of cancer-related death worldwide. Recent advancements in targeted therapies and immunotherapies have achieved remarkable success. However, patient responses to treatments with lung cancer vary substantially. The mutation status of driver genes can direct personalized treatment, but their prognostic value and treatment efficacy are limited. In this study, we developed a statistical framework named Genomic Aberration-Derived Signature for Patient Stratification (GASPS) to characterize the transcriptomic deregulation of driver genomic aberrations and stratify patients. By applying GASPS to The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) data, we developed gene signatures for 38 driver genomic aberrations, including gene mutations, amplifications, and deletions. These signatures were applied to independent lung cancer transcriptomic datasets containing a total of 2,226 patient samples. Our results indicated that these driver gene signatures are much more prognostic than their corresponding genomic mutations. Interestingly, the two EGFR-related signatures characterizing EGFR mutation and amplification, respectively, exhibited contrasting associations with prognosis, treatment response, and immune infiltration in the tumor microenvironment. Moreover, the STK11 mutation signature, rather than the mutation status, was found to be predictive of the response and long-term benefit of patients treated with immune checkpoint blockade therapy in lung cancer. This framework is readily applicable to most cancer types using existing data to improve prognostic risk assessment and treatment efficacy by guiding personalized therapies.

PMID:40909579 | PMC:PMC12407784 | DOI:10.1101/2025.08.21.671519

bioRxiv [Preprint]. 2025 Aug 25:2025.08.21.671519. doi: 10.1101/2025.08.21.671519.

ABSTRACT

Lung cancer is the most common cause of cancer-related death worldwide. Recent advancements in targeted therapies and immunotherapies have achieved remarkable success. However, patient responses to treatments with lung cancer vary substantially. The mutation status of driver genes can direct personalized treatment, but their prognostic value and treatment efficacy are limited. In this study, we developed a statistical framework named Genomic Aberration-Derived Signature for Patient Stratification (GASPS) to characterize the transcriptomic deregulation of driver genomic aberrations and stratify patients. By applying GASPS to The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) data, we developed gene signatures for 38 driver genomic aberrations, including gene mutations, amplifications, and deletions. These signatures were applied to independent lung cancer transcriptomic datasets containing a total of 2,226 patient samples. Our results indicated that these driver gene signatures are much more prognostic than their corresponding genomic mutations. Interestingly, the two EGFR-related signatures characterizing EGFR mutation and amplification, respectively, exhibited contrasting associations with prognosis, treatment response, and immune infiltration in the tumor microenvironment. Moreover, the STK11 mutation signature, rather than the mutation status, was found to be predictive of the response and long-term benefit of patients treated with immune checkpoint blockade therapy in lung cancer. This framework is readily applicable to most cancer types using existing data to improve prognostic risk assessment and treatment efficacy by guiding personalized therapies.

PMID:40909579 | PMC:PMC12407784 | DOI:10.1101/2025.08.21.671519

Discov Oncol. 2025 Jan 28;16(1):96. doi: 10.1007/s12672-025-01841-8.

ABSTRACT

BACKGROUND: Pancreatic cancer (PAC) has a complex tumor immune microenvironment, and currently, there is a lack of accurate personalized treatment. Establishing a novel consensus machine learning driven signature (CMLS) that offers a unique predictive model and possible treatment targets for this condition was the goal of this study.

METHODS: This study integrated multiple omics data of PAC patients, applied ten clustering techniques and ten machine learning approaches to construct molecular subtypes for PAC, and created a new CMLS.

RESULTS: Using multi-omics clustering, we discovered two cancer subtypes (CSs) associated with prognosis, among which CS1 exhibited poor prognostic outcomes. Subsequently, 13 central genes were identified through screening, constituting CMLS with a significant prognostic ability. The low CMLS group had a better prognosis and was more likely to possess a "hot" tumor phenotype. The prognosis for the high CMLS group was dismal. Still, the tumor mutation burden (TMB) and tumor neoantigen burden (TNB) levels in this group of patients were higher than in the low CMLS group, which were more favorable for immune therapy response.

CONCLUSION: This study emphasizes that CMLS provides a beneficial instrument for early prediction of patient prognosis and screening of probable patients appropriate for immunotherapy and has broad implications for clinical practice.

PMID:39873820 | PMC:PMC11775367 | DOI:10.1007/s12672-025-01841-8