Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers

Abstract Metabolic reprogramming, vital for cancer cells to adapt to the altered microenvironment, remains a topic requiring further investigation for different tumor types. Our study aims to elucidate shared metabolic reprogramming across breast (BRC), colorectal (CRC), and lung (LUC) cancers. Leve...

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Main Authors: Jiyauddin Khan, Chanchal Bareja, Kountay Dwivedi, Ankit Mathur, Naveen Kumar, Daman Saluja
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85366-8
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author Jiyauddin Khan
Chanchal Bareja
Kountay Dwivedi
Ankit Mathur
Naveen Kumar
Daman Saluja
author_facet Jiyauddin Khan
Chanchal Bareja
Kountay Dwivedi
Ankit Mathur
Naveen Kumar
Daman Saluja
author_sort Jiyauddin Khan
collection DOAJ
description Abstract Metabolic reprogramming, vital for cancer cells to adapt to the altered microenvironment, remains a topic requiring further investigation for different tumor types. Our study aims to elucidate shared metabolic reprogramming across breast (BRC), colorectal (CRC), and lung (LUC) cancers. Leveraging gene expression data from the Gene Expression Omnibus and various bioinformatics tools like MSigDB, WebGestalt, String, and Cytoscape, we identified key/hub metabolism-related genes (MRGs) and their interactions. The functional characteristics including survival parameters and expression of the key MRGs were analyzed and validated through Gene Expression Profiling Interactive Analysis 2 and qRT-PCR. In addition, we employed machine learning algorithms such as k-nearest neighbours (KNN), support vector regressor (SVR), and extreme gradient boosting (XGBoost) to assess MRGs’ effectiveness in predicting overall patient survival. Among 11,384 DEGs analyzed, 540 overlapped across BRC, CRC, and LUC, with 46 MRGs and 20 key/hub MRGs involved in all studied cancer types. Of these, 11 key MRGs were prognostically significant. The qRT-PCR validation of key MRGs in specific cancer cell lines confirmed their expression profiles, with some showing cell-type-specific patterns. SVR exhibited remarkable accuracy in predicting overall survival, emphasizing its clinical utility. Our integrated approach combining bioinformatics analyses and experimental validations underscores the potential of MRGs as biomarkers for metabolic therapies, with machine learning models enhancing predictive capabilities for patient outcomes.
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spelling doaj-art-4a340724cd5d49a0888fead0364d323d2025-01-12T12:17:37ZengNature PortfolioScientific Reports2045-23222025-01-0115111910.1038/s41598-025-85366-8Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancersJiyauddin Khan0Chanchal Bareja1Kountay Dwivedi2Ankit Mathur3Naveen Kumar4Daman Saluja5Dr B R Ambedkar Center for Biomedical Research, University of DelhiDr B R Ambedkar Center for Biomedical Research, University of DelhiDepartment of Computer Science, FacultyofMathematicalSciences, University of DelhiDr B R Ambedkar Center for Biomedical Research, University of DelhiDepartment of Computer Science, FacultyofMathematicalSciences, University of DelhiDr B R Ambedkar Center for Biomedical Research, University of DelhiAbstract Metabolic reprogramming, vital for cancer cells to adapt to the altered microenvironment, remains a topic requiring further investigation for different tumor types. Our study aims to elucidate shared metabolic reprogramming across breast (BRC), colorectal (CRC), and lung (LUC) cancers. Leveraging gene expression data from the Gene Expression Omnibus and various bioinformatics tools like MSigDB, WebGestalt, String, and Cytoscape, we identified key/hub metabolism-related genes (MRGs) and their interactions. The functional characteristics including survival parameters and expression of the key MRGs were analyzed and validated through Gene Expression Profiling Interactive Analysis 2 and qRT-PCR. In addition, we employed machine learning algorithms such as k-nearest neighbours (KNN), support vector regressor (SVR), and extreme gradient boosting (XGBoost) to assess MRGs’ effectiveness in predicting overall patient survival. Among 11,384 DEGs analyzed, 540 overlapped across BRC, CRC, and LUC, with 46 MRGs and 20 key/hub MRGs involved in all studied cancer types. Of these, 11 key MRGs were prognostically significant. The qRT-PCR validation of key MRGs in specific cancer cell lines confirmed their expression profiles, with some showing cell-type-specific patterns. SVR exhibited remarkable accuracy in predicting overall survival, emphasizing its clinical utility. Our integrated approach combining bioinformatics analyses and experimental validations underscores the potential of MRGs as biomarkers for metabolic therapies, with machine learning models enhancing predictive capabilities for patient outcomes.https://doi.org/10.1038/s41598-025-85366-8Cancer metabolismBreast cancerColorectal cancerLung cancerMetabolism-related genesMachine learning
spellingShingle Jiyauddin Khan
Chanchal Bareja
Kountay Dwivedi
Ankit Mathur
Naveen Kumar
Daman Saluja
Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
Scientific Reports
Cancer metabolism
Breast cancer
Colorectal cancer
Lung cancer
Metabolism-related genes
Machine learning
title Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
title_full Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
title_fullStr Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
title_full_unstemmed Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
title_short Identification and validation of a metabolic-related gene risk model predicting the prognosis of lung, colon, and breast cancers
title_sort identification and validation of a metabolic related gene risk model predicting the prognosis of lung colon and breast cancers
topic Cancer metabolism
Breast cancer
Colorectal cancer
Lung cancer
Metabolism-related genes
Machine learning
url https://doi.org/10.1038/s41598-025-85366-8
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