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FDX1 as a predictive biomarker and therapeutic target for lymph node metastasis in gastric cancer
Clin Exp Med. 2026 May 10. doi: 10.1007/s10238-026-02160-0. Online ahead of print.
ABSTRACT
The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation, immunity, drug sensitivity, and prognostic value of CRGs in GCLM using TCGA and GEO cohorts. Consensus clustering was performed to identify CRG subtypes, with differences characterized by multi-omics analysis. A CRG-based prognostic risk score and immune score were constructed for individualized assessment, and the role of CRGs was validated through in vitro and in vivo experiments. Consensus clustering revealed that CRGs were significantly enriched in biological processes related to mitosis and energy metabolism, as well as in immune-related and cancer-associated pathways. Four distinct CRG subtypes were identified, showing marked differences in expression profiles, prognosis, genetic alterations, TIME, and chemotherapeutic drug sensitivity. We developed an exploratory CRG-based prognostic risk score for preliminary individualized assessment, and the functional relevance of CRGs in GCLM was further validated through in vitro experiments. Among these, FDX1, LIAS, DLAT, MTF1, and GLS were identified as key determinants of overall survival in patients with GCLM, with FDX1 emerging as a potential independent prognostic factor. Notably, upregulation of FDX1 significantly suppressed lymph node metastasis of gastric cancer cells in a mouse popliteal lymph node metastasis model. Our data uncovers FDX1 might be a potential favorable prognostic factors in GCLM patients. These findings may improve our understanding of CRGs in GCLM and provide new in-sights for assessing prognosis and developing more effective treatment strategies.
PMID:42107026 | DOI:10.1007/s10238-026-02160-0
A Data-driven Approach for Biomarker Discovery based on U-centered Distance Correlation Network: Multi-omics Warning Signals for Non-small Cell Lung Cancer
Comb Chem High Throughput Screen. 2026 Mar 27. doi: 10.2174/0113862073445368260131002109. Online ahead of print.
ABSTRACT
INTRODUCTION/OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Alterations in metabolic activities play important roles in NSCLC development, wherein related genes and metabolites interact with each other, involving multiple forms.
METHODS: To comprehensively understand the pathogenic mechanisms and improve the performance of clinical early, precise diagnosis, this study proposed a data-driven approach for biomarker discovery based on U-centered distance correlation network (DCN) to investigate NSCLC metabolism-related reactions. In DCN, changes in molecular relationships during NSCLC initiation and progression are measured using the t-statistics of U-centered distance correlation for network construction, in which prospective warning signals representing NSCLC onset can be identified without human intervention. Additionally, the network construction criterion in DCN can precisely and effectively capture both linear and nonlinear molecular relationships in simple and biologically relevant manners.
RESULTS: DCN was successfully employed to analyze NSCLC metabolism-related metabolomics and genomics datasets. Statistical analyses confirmed that compared with other algorithms, the gene and metabolite biomarker panels identified by DCN provided more reliable diagnostic capabilities for clinical NSCLC detection. Biological analyses revealed that disturbed energy metabolism and lipid metabolism occurred during tumor cell proliferation and growth in NSCLC patients.
DISCUSSION: The gene ASPA and metabolite aspartic acid were significantly decreased in NSCLC samples, suggesting that the corresponding amino acid metabolic activities were intricately linked to NSCLC progression.
CONCLUSION: These findings demonstrated that DCN can further facilitate NSCLC studies to improve clinical outcomes in patients.
PMID:41937706 | DOI:10.2174/0113862073445368260131002109
A Data-driven Approach for Biomarker Discovery based on U-centered Distance Correlation Network: Multi-omics Warning Signals for Non-small Cell Lung Cancer
Comb Chem High Throughput Screen. 2026 Mar 27. doi: 10.2174/0113862073445368260131002109. Online ahead of print.
ABSTRACT
INTRODUCTION/OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Alterations in metabolic activities play important roles in NSCLC development, wherein related genes and metabolites interact with each other, involving multiple forms.
METHODS: To comprehensively understand the pathogenic mechanisms and improve the performance of clinical early, precise diagnosis, this study proposed a data-driven approach for biomarker discovery based on U-centered distance correlation network (DCN) to investigate NSCLC metabolism-related reactions. In DCN, changes in molecular relationships during NSCLC initiation and progression are measured using the t-statistics of U-centered distance correlation for network construction, in which prospective warning signals representing NSCLC onset can be identified without human intervention. Additionally, the network construction criterion in DCN can precisely and effectively capture both linear and nonlinear molecular relationships in simple and biologically relevant manners.
RESULTS: DCN was successfully employed to analyze NSCLC metabolism-related metabolomics and genomics datasets. Statistical analyses confirmed that compared with other algorithms, the gene and metabolite biomarker panels identified by DCN provided more reliable diagnostic capabilities for clinical NSCLC detection. Biological analyses revealed that disturbed energy metabolism and lipid metabolism occurred during tumor cell proliferation and growth in NSCLC patients.
DISCUSSION: The gene ASPA and metabolite aspartic acid were significantly decreased in NSCLC samples, suggesting that the corresponding amino acid metabolic activities were intricately linked to NSCLC progression.
CONCLUSION: These findings demonstrated that DCN can further facilitate NSCLC studies to improve clinical outcomes in patients.
PMID:41937706 | DOI:10.2174/0113862073445368260131002109