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We developed a novel computational approach to identify cancer-related risk metabolic subpathways (CMSubpathway). By leveraging the topology of large-scale metabolic pathway gene networks, we initially identified metabolic subpathways and then refined them by taking into account pathway activity dysregulation, prognostic efficacy, and classification performance. We employed the CMSubpathway to extensively identify cancer-related metabolic subpathways across 21 cancer types. Ultimately, 12 risk metabolic subpathways were identified in six cancer types. Subsequently, the 12 overlapping genes of risk metabolic subpathways were identified as the core metabolic module genes. Utilizing the public CRISPR knockout screening datasets sourced from DepMap, we further supported our hypothesis that the essential roles of ADH5, ALDH1B1, and ALDH7A1 in breast cancer cell growth and development. The core metabolic module and its associated genes exhibited significant down-regulation at both the transcriptome and proteome levels based on data from tissues, blood, and single cells. The activity of this core metabolic module was associated with the immune infiltration levels of multiple immune cells, especially T cells. Notably, an abnormal core metabolic module was observed in CD8 T cell subtypes, with the stem-like CD8 T cell subtype showing high metabolic activity and exhaustion markers. Thus, we established a method for identifying risk metabolic subpathways in cancers, which helps to identify more precise biomarkers for cancer patients.<\/jats:p>","DOI":"10.3390\/ijms27104246","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Characterization of Cancer-Related Risk Metabolic Subpathways Reveal Their Functional Significance in Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Hongying","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxing","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Opto-Electronics, Harbin Institute of Technology, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhe","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiting","family":"Fei","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-0315","authenticated-orcid":false,"given":"Wan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-8513","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cmet.2023.12.003","article-title":"Metabolic switch regulates lineage plasticity and induces synthetic lethality in triple-negative breast cancer","volume":"36","author":"Zhang","year":"2024","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165721","DOI":"10.1016\/j.bbadis.2020.165721","article-title":"Metabolic reprogramming and disease progression in cancer patients","volume":"1866","author":"Torresano","year":"2020","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1158\/0008-5472.CAN-22-3059","article-title":"Metabolic reprogramming driven by IGF2BP3 promotes acquired resistance to EGFR inhibitors in non\u2013small cell lung cancer","volume":"83","author":"Lin","year":"2023","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12951-022-01314-y","article-title":"Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA","volume":"20","author":"Chen","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 polarization","volume":"877","author":"Chen","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.cmet.2020.05.004","article-title":"Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization","volume":"31","author":"Zhang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1093\/nar\/gkt161","article-title":"Subpathway-GM: Identification of metabolic subpathways via joint power of interesting genes and metabolites and their topologies within pathways","volume":"41","author":"Li","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"bbaa413","DOI":"10.1093\/bib\/bbaa413","article-title":"CNA2Subpathway: Identification of dysregulated subpathway driven by copy number alterations in cancer","volume":"22","author":"Sheng","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Han, X., Wang, D., Zhao, P., Liu, C., Hao, Y., Chang, L., Zhao, J., Zhao, W., Mu, L., and Wang, J. (2020). Inference of subpathway activity profiles reveals metabolism abnormal subpathway regions in glioblastoma multiforme. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01549"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41586-019-0977-x","article-title":"Breast cancer cells rely on environmental pyruvate to shape the metastatic niche","volume":"568","author":"Elia","year":"2019","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41588-024-01662-5","article-title":"Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression","volume":"56","author":"Hu","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33262","DOI":"10.1038\/srep33262","article-title":"Subpathway-CorSP: Identification of metabolic subpathways via integrating expression correlations and topological features between metabolites and genes of interest within pathways","volume":"6","author":"Feng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/s42255-023-00817-8","article-title":"A multimodal atlas of tumour metabolism reveals the architecture of gene\u2013metabolite covariation","volume":"5","author":"Benedetti","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature24057","article-title":"Glucose feeds the TCA cycle via circulating lactate","volume":"551","author":"Hui","year":"2017","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.cell.2017.09.019","article-title":"Lactate metabolism in human lung tumors","volume":"171","author":"Faubert","year":"2017","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: How does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23111","DOI":"10.1074\/jbc.M202487200","article-title":"Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis","volume":"277","author":"Lu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_19","first-page":"3930","article-title":"Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-pharmtox-052220-105907","article-title":"Non-P450 drug-metabolizing enzymes: Contribution to drug disposition, toxicity, and development","volume":"62","author":"Fukami","year":"2022","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_21","first-page":"587","article-title":"Alcohol dehydrogenase-1B represses the proliferation, invasion and migration of breast cancer cells by inactivating the mitogen-activated protein kinase signalling pathway","volume":"74","author":"Jiang","year":"2023","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xue, Y., Wang, M., Zhong, D., Tong, N., Chu, H., Sheng, X., and Zhang, Z. (2012). ADH1C Ile350Val polymorphism and cancer risk: Evidence from 35 case\u2013control studies. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037227"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101534","DOI":"10.1016\/j.tranon.2022.101534","article-title":"Energy metabolism pathways in breast cancer progression: The reprogramming, crosstalk, and potential therapeutic targets","volume":"26","author":"Zheng","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_24","first-page":"453","article-title":"Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release","volume":"39","author":"Goetze","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.1172\/JCI69589","article-title":"Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function","volume":"123","author":"Sukumar","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1158\/0008-5472.CAN-22-0090","article-title":"Single-cell transcriptome profiling reveals intratumoral heterogeneity and molecular features of ductal carcinoma in situ","volume":"82","author":"Tokura","year":"2022","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.omtn.2022.11.019","article-title":"The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis","volume":"30","author":"Wang","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-019-1836-5","article-title":"An intra-tumoral niche maintains and differentiates stem-like CD8 T cells","volume":"576","author":"Jansen","year":"2019","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/s42255-020-00280-9","article-title":"Metabolic and epigenetic regulation of T-cell exhaustion","volume":"2","author":"Franco","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41574-021-00487-0","article-title":"Metabolic pathways in obesity-related breast cancer","volume":"17","author":"Brown","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41577-021-00539-6","article-title":"Cellular networks controlling T cell persistence in adoptive cell therapy","volume":"21","author":"Chan","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41577-019-0223-7","article-title":"Precursor exhausted T cells: Key to successful immunotherapy?","volume":"20","author":"Kallies","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Frisardi, V., Canovi, S., Vaccaro, S., and Frazzi, R. (2023). The significance of microenvironmental and circulating lactate in breast cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015369"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101454","DOI":"10.1016\/j.redox.2020.101454","article-title":"Lactate as a fulcrum of metabolism","volume":"35","author":"Brooks","year":"2020","journal-title":"Redox Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12943-021-01316-8","article-title":"The cancer metabolic reprogramming and immune response","volume":"20","author":"Xia","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1093\/bioinformatics\/btp167","article-title":"KEGGgraph: A graph approach to KEGG PATHWAY in R and bioconductor","volume":"25","author":"Zhang","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D199","DOI":"10.1093\/nar\/gkac984","article-title":"LncTarD 2.0: An updated comprehensive database for experimentally-supported functional lncRNA\u2013target regulations in human diseases","volume":"51","author":"Zhao","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6322","DOI":"10.1038\/s41467-020-20059-6","article-title":"Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma","volume":"11","author":"Zhou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41422-022-00635-9","article-title":"Evolutionarily conservative and non-conservative regulatory networks during primate interneuron development revealed by single-cell RNA and ATAC sequencing","volume":"32","author":"Zhao","year":"2022","journal-title":"Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/bioinformatics\/btp692","article-title":"RNA-Seq gene expression estimation with read mapping uncertainty","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huang, J., Sun, H., Liu, Y., Song, Q., and Weninger, T. (2011). Towards online multiresolution community detection in large-scale networks. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023829"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Candia, J., and Ferrucci, L. (2024). Assessment of Gene Set Enrichment Analysis using curated RNA-seq-based benchmarks. PLoS ONE, 19.","DOI":"10.1101\/2024.01.10.575094"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Acharya, S., Kossinna, P., Zhang, Q., and Guo, J. (2025). Stabilized marker gene identification and functional annotation from single-cell transcriptomic data. PLoS Comput. Biol., 21.","DOI":"10.1371\/journal.pcbi.1013574"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e70581","DOI":"10.1002\/mco2.70581","article-title":"Regulation and Mechanism of Deleted in Breast Cancer-1 on Dendritic Cell Function in Systemic Lupus Erythematosus","volume":"7","author":"Xiao","year":"2026","journal-title":"MedComm"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"H\u00e4nzelmann, S., Castelo, R., and Guinney, J. (2013). GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-7"},{"key":"ref_46","first-page":"41","article-title":"Applications of support vector machine (SVM) learning in cancer genomics","volume":"15","author":"Huang","year":"2018","journal-title":"Cancer Genom. Proteom."},{"key":"ref_47","unstructured":"Meyer, D., Dimitriadou, E., Hornik, K., Weingessel, A., and Leisch, F. (2026, May 05). e1071: Misc Functions of the Department of Statistics, Probability Theory Group (Formerly: E1071), TU Wien. Available online: https:\/\/cran.r-project.org\/web\/packages\/e1071\/index.html."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ning, Z., Yu, S., Zhao, Y., Sun, X., Wu, H., and Yu, X. (2021). Identification of miRNA-mediated subpathways as prostate cancer biomarkers based on topological inference in a machine learning process using integrated gene and miRNA expression data. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.656526"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.1038\/s41467-019-13588-2","article-title":"Genetic determinants of the molecular portraits of epithelial cancers","volume":"10","author":"Xia","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D870","DOI":"10.1093\/nar\/gkac947","article-title":"CellMarker 2.0: An updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data","volume":"51","author":"Hu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.7150\/ijms.107691","article-title":"Large-scale genomic-wide CRISPR screening revealed PRC1 as a tumor essential candidate in clear cell renal cell carcinoma","volume":"22","author":"Li","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1101\/gr.278431.123","article-title":"Accurate estimation of pathway activity in single cells for clustering and differential analysis","volume":"34","author":"Davis","year":"2024","journal-title":"Genome Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1126\/science.aax0249","article-title":"Single-cell transcriptional diversity is a hallmark of developmental potential","volume":"367","author":"Gulati","year":"2020","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:18:15Z","timestamp":1779164295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":54,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104246"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104246","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]}}}