{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:36Z","timestamp":1760059896005,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Inner Mongolia","award":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"],"award-info":[{"award-number":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"]}]},{"name":"National Natural Science Foundation of China Grant Program","award":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"],"award-info":[{"award-number":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"]}]},{"name":"basic scientific research funding for universities directly under Inner Mongolia Autonomous Region","award":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"],"award-info":[{"award-number":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"]}]},{"name":"Innovation Support Program for Overseas Returnees from Inner Mongolia Autonomous Region","award":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"],"award-info":[{"award-number":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"]}]},{"name":"2025 Inner Mongolia Key Laboratory of Life Health and Bioinformatics Project","award":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"],"award-info":[{"award-number":["2022LHMS03015","2024MS03054","2024JQ10","62371265","62261043","2023RCTD023","2025KYPT0135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Background: Epigenomic instability accelerates mutations in tumor suppressor genes and oncogenes, contributing to malignant transformation. Histone modifications, particularly methylation and acetylation, significantly influence tumor biology, with chromo-, bromo-, and Tudor domain-containing proteins mediating these changes. This study investigates how genes encoding these domain-containing proteins affect colorectal cancer (CRC) prognosis. Methods: Using CRC data from the GSE39582 and TCGA datasets, we identified domain-related genes via GeneCards and developed a prognostic signature using LASSO-COX regression. Patients were classified into high- and low-risk groups, and comparisons were made across survival, clinical features, immune cell infiltration, immunotherapy responses, and drug sensitivity predictions. Single-cell analysis assessed gene expression in different cell subsets. Results: Four domain-related genes (AKAP1, ORC1, CHAF1A, and UHRF2) were identified as a prognostic signature. Validation confirmed their prognostic value, with significant differences in survival, clinical features, immune patterns, and immunotherapy responses between the high- and low-risk groups. Drug sensitivity analysis revealed top candidates for CRC treatment. Single-cell analysis showed varied expression of these genes across cell subsets. Conclusions: This study presents a novel prognostic signature based on domain-related genes that can predict CRC severity and offer insights into immune dynamics, providing a promising tool for personalized risk assessment in CRC.<\/jats:p>","DOI":"10.3390\/computation13070171","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:33:47Z","timestamp":1752748427000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction and Evaluation of a Domain-Related Risk Model for Prognosis Prediction in Colorectal Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiangjun","family":"Cui","sequence":"first","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China"},{"name":"Inner Mongolia Key Laboratory of Life Health and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou 014010, China"}]},{"given":"Yongqiang","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China"},{"name":"Inner Mongolia Key Laboratory of Life Health and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou 014010, China"}]},{"given":"Guoqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China"},{"name":"Inner Mongolia Key Laboratory of Life Health and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou 014010, China"}]},{"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China"},{"name":"Inner Mongolia Key Laboratory of Life Health and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou 014010, China"}]},{"given":"Zhenhua","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Economics and Management, Inner Mongolia University of Science and Technology, Baotou 014010, China"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1001\/jamaoncol.2020.2592","article-title":"Benign vs. Malignant Tumors","volume":"6","author":"Patel","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15065","DOI":"10.1038\/nrdp.2015.65","article-title":"Colorectal cancer","volume":"1","author":"Kuipers","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Baylin, S.B., and Jones, P.A. (2016). Epigenetic Determinants of Cancer. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a019505"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s12253-019-00663-8","article-title":"Histone Modifications and their Role in Colorectal Cancer","volume":"26","author":"Qin","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Boyson, S.P., Gao, C., Quinn, K., Boyd, J., Paculova, H., Frietze, S., and Glass, K.C. (2021). Functional roles of bromodomain proteins in cancer. Cancers, 13.","DOI":"10.3390\/cancers13143606"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.ijbiomac.2019.03.162","article-title":"Investigating the structural features of chromodomain proteins in the human genome and predictive impacts of their mutations in cancers","volume":"131","author":"Dahiya","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Novillo, A., Fern\u00e1ndez-Santander, A., Gaibar, M., Gal\u00e1n, M., Romero-Lorca, A., El Abdellaoui-Soussi, F., and Arco, P.G.-D. (2021). Role of chromodomain-helicase-DNA-binding protein 4 (CHD4) in breast cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.633233"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.tibs.2013.08.002","article-title":"Tudor: A versatile family of histone methylation \u2018readers\u2019","volume":"38","author":"Lu","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.molonc.2015.10.013","article-title":"An integrated genomic analysis of Tudor domain-containing proteins identifies PHD finger protein 20-like 1 (PHF20L1) as a candidate oncogene in breast cancer","volume":"10","author":"Jiang","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6898","DOI":"10.7150\/thno.78377","article-title":"The palmitoylation of AEG-1 dynamically modulates the progression of hepatocellular carcinoma","volume":"12","author":"Zhou","year":"2022","journal-title":"Theranostics"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sun, H., and Zhang, H. (2024). Lysine Methylation-Dependent Proteolysis by the Malignant Brain Tumor (MBT) Domain Proteins. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042248"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cheng, Q., Ji, W., Lv, Z., Wang, W., Xu, Z., Chen, S., Zhang, W., Shao, Y., Liu, J., and Yang, Y. (2024). Comprehensive analysis of PHF5A as a potential prognostic biomarker and therapeutic target across cancers and in hepatocellular carcinoma. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12620-z"},{"key":"ref_13","unstructured":"Carlson, M. (2012). hgu133plus2.db: Affymetrix Affymetrix HG-U133_Plus_2 Array Annotation Data (chip hgu133plus2), Fred Hutchinson Cancer Center. R package version 3.13.0 [Computer software]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"14","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_16","unstructured":"Carlson, M. (2023). org.Hs.eg.db: Genome Wide Annotation for Human, Fred Hutchinson Cancer Center. R package version 3.17.0 [Computer software]."},{"key":"ref_17","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, J., and Jin, Z. (2021). ggrisk: Risk Score Plot for Cox Regression, Schr\u00f6dingerplatz. R package version 1.3 [Computer software].","DOI":"10.32614\/CRAN.package.ggrisk"},{"key":"ref_22","unstructured":"Therneau, T. (2024). A Package for Survival Analysis in R, Schr\u00f6dingerplatz. R package version 3.8-3 [Computer software]."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Therneau, T.M., and Grambsch, P.M. (2000). Modeling Survival Data: Extending the Cox Model, Springer.","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"ref_24","unstructured":"Heagerty, P.J., and Saha-Chaudhuri, P.B.P. (2022). survivalROC: Time-Dependent ROC Curve Estimation from Censored Survival Data, Schr\u00f6dingerplatz. R package version 1.0.3.1 [Computer software]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: Efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1158\/2326-6066.CIR-18-0436","article-title":"Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures","volume":"7","author":"Zeng","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_28","unstructured":"Yoshihara, K., Kim, H., and Verhaak, R.G. (2016). estimate: Estimate of Stromal and Immune Cells in Malignant Tumor Tissues from Expression Data, Schr\u00f6dingerplatz. R package version 1.0.13\/r21 [Computer software]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1158\/1078-0432.CCR-20-2166","article-title":"An immune-related gene prognostic index for head and neck squamous cell carcinoma","volume":"27","author":"Chen","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_30","unstructured":"Nickles, D., and Bourgon, R. (2019). IMvigor210CoreBiologies: Data Processing and Analysis Code for the Manuscript Mariathasan et al., TGF-b Attenuates Tumor Response to PD-L1 Blockade by Contributing to Exclusion of T Cells, Genentech. R package version 1.0.0 [Computer software]."},{"key":"ref_31","unstructured":"Maeser, D., and Gruener, R. (2024). oncoPredict: Drug Response Modeling and Biomarker Discovery, Schr\u00f6dingerplatz. R package version 1.2 [Computer software]."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Maeser, D., Gruener, R.F., and Huang, R.S. (2021). oncoPredict: An R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data. Brief. Bioinform., 22.","DOI":"10.1093\/bib\/bbab260"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial reconstruction of single-cell gene expression data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_40","unstructured":"Aibar, S. (2016). AUCell: Analysis of \u2018Gene Set\u2019 Activity in Single-Cell RNA-seq Data, Fred Hutchinson Cancer Center. [Computer software]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2174\/1389203717666160122120521","article-title":"The functions of histone modification enzymes in cancer","volume":"17","author":"Wang","year":"2016","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1002\/ijc.33036","article-title":"UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt\/\u03b2-catenin signaling","volume":"147","author":"Li","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.2147\/IJGM.S405419","article-title":"The Role of RNA Methylation Modification Related Genes in Prognosis and Immunotherapy of Colorectal Cancer","volume":"16","author":"Lin","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1080\/15592294.2017.1314423","article-title":"UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures","volume":"12","author":"Liu","year":"2017","journal-title":"Epigenetics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/15384101.2024.2353553","article-title":"UHRF2 accumulates in early G(1)-phase after serum stimulation or mitotic exit to extend G(1) and total cell cycle length","volume":"23","author":"Wang","year":"2024","journal-title":"Cell Cycle"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12950","DOI":"10.1073\/pnas.1203701109","article-title":"Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1","volume":"109","author":"Arita","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3892\/or.2014.3035","article-title":"Ubiquitin-like with PHD and ring finger domains 2 is a predictor of survival and a potential therapeutic target in colon cancer","volume":"31","author":"Lu","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chalbatani, G.M., Gharagouzloo, E., Malekraeisi, M.A., Azizi, P., Ebrahimi, A., Hamblin, M.R., Mahmoodzadeh, H., Elkord, E., Miri, S.R., and Sanati, M.H. (2023). The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-46620-z"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wu, L., Chen, H., and Yang, C. (2023). Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer. BMC Med. Genom., 16.","DOI":"10.1186\/s12920-023-01691-9"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/01635581.2018.1540715","article-title":"Butyrate-induced in vitro colonocyte differentiation network model identifies ITGB1, SYK, CDKN2A, CHAF1A, and LRP1 as the prognostic markers for colorectal cancer recurrence","volume":"71","author":"Dasgupta","year":"2019","journal-title":"Nutr. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbrc.2014.05.006","article-title":"Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer","volume":"449","author":"Wu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-2187-8-10","article-title":"Differential PKA activation and AKAP association determines cell fate in cancer cells","volume":"8","author":"Hedrick","year":"2013","journal-title":"J. Mol. Signal"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chowdhury, S., Howell, G.M., Rajput, A., Teggart, C.A., Brattain, L.E., Weber, H.R., Chowdhury, A., Brattain, M.G., and Chandra, D. (2011). Identification of a novel TGFbeta\/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019335"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1158\/0008-5472.CAN-06-0191","article-title":"KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer","volume":"66","author":"Bachet","year":"2006","journal-title":"Cancer Res."},{"key":"ref_55","first-page":"310","article-title":"Prognostic factors in colorectal cancer","volume":"47","author":"Gennari","year":"2000","journal-title":"Hepatogastroenterology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nm.3967","article-title":"The consensus molecular subtypes of colorectal cancer","volume":"21","author":"Guinney","year":"2015","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1200\/JCO.2008.20.6771","article-title":"Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial","volume":"27","author":"Boni","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12935-023-02897-8","article-title":"Exploring the role of pyroptosis in shaping the tumor microenvironment of colorectal cancer by bulk and single-cell RNA sequencing","volume":"23","author":"Ding","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Li, X., Li, J., Li, J., Liu, N., and Zhuang, L. (2024). Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer. BMC Genom., 25.","DOI":"10.1186\/s12864-023-09815-2"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12967-024-04955-9","article-title":"A multi-dimensional approach to unravel the intricacies of lactylation related signature for prognostic and therapeutic insight in colorectal cancer","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"M\u00fcller, D., and Gy\u0151rffy, B. (2022). DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer. Biochim. Biophys. Acta Rev. Cancer, 1877.","DOI":"10.1016\/j.bbcan.2022.188722"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Vuleti\u0107, A., Mirja\u010di\u0107 Martinovi\u0107, K., and Spasi\u0107, J. (2023). Role of Histone Deacetylase 6 and Histone Deacetylase 6 Inhibition in Colorectal Cancer. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010054"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, C., Song, J., Guo, Z., Gong, Y., Zhang, T., Huang, J., Cheng, R., Yu, X., Li, Y., and Chen, L. (2022). EZH2 Inhibitors Suppress Colorectal Cancer by Regulating Macrophage Polarization in the Tumor Microenvironment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.857808"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Conte, M., Di Mauro, A., Capasso, L., Montella, L., De Simone, M., Nebbioso, A., and Altucci, L. (2023). Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15071960"}],"container-title":["Computation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/7\/171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:18Z","timestamp":1760033478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/7\/171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["computation13070171"],"URL":"https:\/\/doi.org\/10.3390\/computation13070171","relation":{},"ISSN":["2079-3197"],"issn-type":[{"type":"electronic","value":"2079-3197"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}