Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer最新文献

{"title":"Lactylation-Related Gene Expression as a Predictor for Lung Adenocarcinoma Prognosis, Microenvironment Characteristics, and Therapeutic Reactions.","authors":"Rui Liu, Zhiqiang Li, Kai Chen, Jinzhi Xu, Jinli Liu","doi":"10.1615/JEnvironPatholToxicolOncol.2025054335","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2025054335","url":null,"abstract":"<p><p>The pursuit of effective immunotherapy for lung adenocarcinoma (LUAD) is ongoing. Lactylation is a promising target for cancer management; yet role of lactylation-related genes (LRGs) in LUAD is still largely unexplored. This study was designed to identify genes related to lactylation in LUAD to assist in prognostic treatment. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and related literature were accessed to download gene expression and clinical information. To screen LRGs and create a prognostic model, univariate Cox, multivariate Cox, and Lasso regression analyses were then employed. Based on the median risk score, patients were categorized into high- and low-risk groups, and survival analysis and model validation were done. A nomogram was created, and its capacity for prediction was assessed by plotting ROC and DCA curves. To build PPI networks, enrichment, immune microenvironment, immunotherapy response, and tumor mutation analyses, and medication prediction were completed on differentially expressed genes between high- and low-risk groups. Prognostic model was built using LRGs associated with LUAD prognosis (HNRNPAB, PSMB2, DDX5, SURF6, HOMER3, ENO2, and HSPA1L). Patients' survival in high-risk group was noticeably lower. Risk scores can be included into a nomogram or be utilized as an independent component for prognosis prediction. These genes were mostly concentrated in cAMP signaling pathway, Neuroactive ligand-receptor interaction, and hormone-related pathways. Immunological milieu of high-risk group was compromised, as evidenced by their lower IPS and higher TIDE scores. There was a chance that AP-24534 (low-risk group) and CGP-082996 (high-risk group) might work. To synthesize, the LRGs-LUAD prognostic model came as a viable instrument for forecasting the prognosis of LUAD patients, bolstering clinical practice in prognostic risk appraisal and patient-specific treatment.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 2","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Medicinal Plant Research for Mitigating Aluminium Toxicity.","authors":"Sanjib Bhattacharya","doi":"10.1615/JEnvironPatholToxicolOncol.2025055710","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025055710","url":null,"abstract":"<p><p>Aluminium is the third common metal of the earth, yet, it is physiologically non-essential and its higher levels on regular exposure can be harmful to the human body, affecting many vital organ systems. Environmental aluminium contamination and toxicity thereof is regarded as a 'silent killer' to the mankind as it is associated with the precipitation of several serious health complications chiefly involving nervous, blood and musculoskeletal systems. Various medicinal plants have been reported to possess aluminium toxicity ameliorative effects. A compilation of research published over the past 21 years on the protective properties of medicinal plants against the toxicity of aluminium is made. Thirty-four such plants reportedly have the ability to mitigate the toxicity of experimental aluminium in animals/cells/tissues leading to marked improvement of aluminium-induced pathophysiological complications, by multiple mechanisms; the prime typical modes inter alia are modulation of oxidative stress-inflammatory pathways and anti-cholinesterase activity. Thus, recent advances in this field of study may help to develop a potential nutraceutical or phytotherapeutic candidate against aluminium toxicity and neurodegenerative diseases for humans.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"71-84"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor Effect of 5-Aminolevulinic Acid Methyl Ester-Mediated Photodynamic Therapy on Local Skin Melanoma and Its Metastasized Tumor, in Relation with Antitumor Immunity.","authors":"Mima Danzeng, Li Anxin, Gongsang Duoji, Xiao Pudroma","doi":"10.1615/JEnvironPatholToxicolOncol.2025058961","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025058961","url":null,"abstract":"<p><p>Objective of the present study is to investigate the effect of photodynamic therapy (PDT) mediated by 5-aminolevulinic acid methyl ester hydrochloride (ALA-Me) on inhibiting the primary tumor growth and metastasis of melanoma, in relation with antitumor immunity. Although the effect of ALA-PDT on lymphocyte T cells has been extensively studied, there are limited publications about ALA-PDT effect on B cells and NK cells. In particular, at present there is no study of ALA-Me-PDT on B cells and NK cells. Therefore, in order to only investigate this aspect, we have employed T-lymphocyte deficient Balb/c nude mice.</p><p><strong>Methods: </strong>A non-pigmented melanoma mouse model, which was challenged with human primary melanoma cells WM266-4, was established in 36 nude mice. When the melanoma grew to size of (0.4 ȕ 0.4) cm2, the 36 mice were randomly divided into 4 groups, i.e., ALA-Me intravenous (i.v.) injection-PDT, ALA-Me intraperitoneal (i.p.) injection-PDT, ALA-Me topical application-PDT and control group without any treatment. The dose for systemic administration (i.v. and i.p.) of ALA-Me was 250 mg/kg. For topical application of ALA-Me, a cream with 25 mg/cm2 was smeared on the tumor tissue. The tumor site was irradiated by the red light from LEDs lamp with fluence rate 90 mW/cm2 and energy rate 50 J/cm2.</p><p><strong>Results: </strong>The inhibitory effects on both tumor growth and metastasis were observed after all three treatments mentioned above. In terms of inhibiting tumor growth, there was a significant difference in the volume of tumor between the treatment groups and the control group (P < 0.05). Furthermore, a very significant (P < 0.01) inhibitory effect on tumor lung metastasis was found after the three treatments. Moreover, the ALA-Me-PDT-induced immune response was also observed by means of increase of immune cells NK cells in the spleen of the T cell-deficient nude mice.</p><p><strong>Conclusion: </strong>ALA-Me-PDT had significant inhibitory effects both on local tumor growth and distant lung metastasis of melanoma. There was also significant antitumor immunity caused by ALA-Me-PDT. Results of the present study provide a potential possibility for ALA-Me-PDT in the treatment of skin melanoma and its metastasis.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"43-54"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals for Ameliorating Aluminum Toxicity: Dissecting the Mechanisms for Therapeutic Potential.","authors":"Sanjib Bhattacharya","doi":"10.1615/JEnvironPatholToxicolOncol.2025056997","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2025056997","url":null,"abstract":"<p><p>Although aluminum is the third common metal of the earth, it is physiologically nonessential and its higher levels on regular exposure can be harmful to the human body, affecting several vital organ systems. Environmental aluminum contamination and toxicity are therefore regarded as a \"silent killer\" as it is associated with the precipitation of several serious health complications chiefly involving the nervous, blood, and musculoskeletal systems. Various natural products obtained from medicinal plants; that is, phytochemicals have been reported to possess aluminum toxicity ameliorative potential. Still now, there is no comprehensive review in this regard. A compilation of research has been published over the past 21 years on the protective properties of plant-derived phytochemicals against the toxicity of aluminum. Reportedly, 45 phytochemicals of diverse chemical classes mitigate the toxicity of experimental aluminum in animals/cells/tissues, leading to marked reduction of aluminum-induced pathophysiological complications, by multiple mechanisms; the prime typical modes, among others, are modulation of oxidative stress-inflammatory pathways and anti-cholinesterase activity. These recent advances may help to develop a potential nutraceutical or phytomedicinal candidate against aluminum toxicity and neurodegenerative diseases for humans.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 2","pages":"79-97"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"lncRNA FENDRR as a Prognostic Biomarker and Regulator of Bladder Cancer Progression via the miR-18a-5p/ESR1 Axis.","authors":"Chao Gao, Xiliang Cao, Long Miao, Wei Chen, Jin Wei, Lu Lou","doi":"10.1615/JEnvironPatholToxicolOncol.2025056717","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025056717","url":null,"abstract":"<p><p>Recent research highlights the pivotal function of long non-coding RNAs (lncRNAs) in bladder cancer (BCa) progression, emphasizing the need to understand their functions. The clinical significance and molecular mechanisms of lncRNA FENDRR in BCa needed to be elucidated. The Gene Expression Omnibus (GEO) database for BCa-related lncRNAs was screened. Tumor and para cancerous tissues from 118 patients with BCa were collected. Real-time quantitative polymerase chain reaction assessed FENDRR, microRNA (miR)-18a-5p, and estrogen receptor 1 (ESR1) levels. Kaplan-Meier curves assessed FENDRR's prognostic significance. Cell Counting Kit-8, Transwell, and flow cytometry evaluated cell proliferation, migration, invasion, and apoptosis. Dual-Luciferase Reporter and RNA Immunoprecipitation assays revealed miR-18a-5p targeting of FENDRR and ESR1. FENDRR exhibited differential expression in BCa GEO databases. Notably, FENDRR and ESR1 were downregulated, while miR-18a-5p was upregulated in BCa tissues and cell lines. Low FENDRR expression correlated with poor clinical prognosis. Upregulating FENDRR hindered cell proliferation, migration, and invasion while promoting apoptosis; however, miR-18a-5p reversed this suppression. Mechanistically, miR-18a-5p directly targets both FENDRR and ESR1. Our study reveals that low FENDRR expression is a poor prognostic indicator in BCa. FENDRR inhibits miR-18a-5p to upregulate ESR1 and hinder cancer progression, suggesting potential therapeutic targets.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DACT1 as a Potential Therapeutic Target in Gastric Cancer: Insights from Integrative Bioinformatics and Experimental Analysis.","authors":"Rui-Sheng Ke, Bing Bai, Yan-Ling Tu, Kun-Zhai Huang, Fu-Xing Zhang, Zhao-Hui Liu","doi":"10.1615/JEnvironPatholToxicolOncol.2025054852","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025054852","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a significant worldwide health issue, Dapper Antagonist of β-Catenin-1 (DACT1) is a gene implicated in various cancers. Bioinformatics analysis across multiple databases were utilized to investigate DACT1 expression and its correlation with GC prognosis. Subsequent experimental work involved cell culture, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and Western Blot to explore the role of DACT1 in GC cell lines. Bioinformatics analysis revealed that DACT1 was highly expressed and linked to a low overall survival rate in GC. DACT1 expression was linked to epithelial mesenchymal transition (EMT) and Notch signaling pathways, both critical in cancer progression. Experimental validation further demonstrated that the knockdown of DACT1 inhibits GC cell proliferation, migration, the EMT process, and the activity of the Notch signaling pathway. DACT1 may serve as a promising target in GC treatment through its involvement in EMT and Notch signaling. The study provides a foundation for further investigation of DACT1 in GC.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"55-70"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Prognosis, Tumor Microenvironment, and Drug Treatment of Colorectal Cancer Based on Retinoic Acid-Related Genes.","authors":"Yuecheng Wang, Rui Feng, Rui Shang","doi":"10.1615/JEnvironPatholToxicolOncol.2025055211","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025055211","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a serious malignancy. Retinoic acid (RA) can inhibit cancer cell growth, promote cancer cell apoptosis, and hold significant importance for tumor prognosis. We utilized TCGA public data to screen RA-related genes linked with survival. Based on RA-related genes, the CRC prognostic model was generated by Cox regression analysis. Subsequently, immune infiltration analysis, functional enrichment analysis of differentially expressed genes (DEGs), tumor mutation analysis, and drug prediction were carried out based on the high-risk (HR) and low-risk (LR) groups identified in the prognostic model. We identified 10 RA-related genes associated with CRC. A prognostic model was constructed based on RA-related genes. CRC patients were divided into HR and LR groups. Immune infiltration analysis demonstrated that cells such as B cells, iDCs, and mast cells had higher infiltration levels in the LR group (P < 0.05). The results of DEG enrichment analysis of HR and LR groups uncovered that DEGs were mainly enriched in Alcoholism, regionalization, nucleosome, DNA packaging complex, and other biological processes. Drug sensitivity prediction results revealed that AZ628, CGP-082996, CKM, Dasatinib, GNF-2, Saracatinib, Sorafenib, WH-4-023, and WZ-1-84 were more sensitive for patients in the HR group. AKT inhibitor VIII, Gemcitabine, JW-7-52-1, Mitomycin, NSC-87877, PAC-1, Pyrimethamine, QS11, and Roscovitine were more sensitive for those in the LR group. Our project identified correlations between RA-related genes and CRC. The model genes identified are essential indicators for evaluating CRC prognosis and further treating CRC.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"25-41"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA GHET1 Overexpression Facilitates Cancer Progression and Is an Unfavorable Prognosis Factor in Esophageal Cancer.","authors":"Jin Zhang, Yaohua Chen","doi":"10.1615/JEnvironPatholToxicolOncol.2025055268","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025055268","url":null,"abstract":"<p><strong>Aim: </strong>This research sought to estimate the prognostic performance and cellular behaviors of lncRNA GHET1 (gastric carcinoma highly expressed transcript 1) in sufferers of esophageal cancer.</p><p><strong>Method: </strong>GHET1 expression was measured in esophageal cancer through quantitative real-time polymerase chain reaction (qRT-PCR) method. The prognostic performance of GHET1 level was estimated by Kaplan-Meier and Cox regression analyses. The cellular activities of GHET1 on esophageal cancer cells were estimated by transfecting siRNA.</p><p><strong>Results: </strong>The relative abundance of GHET1 was notably elevated in esophageal cancer tissues and cells in respective order (P < 0.001). Abnormal GHET1 expression was notably in relation to differentiation (P = 0.049), LNM (lymph node metastasis, P = 0.002) and TNM (tumor node metastasis, P = 0.015). Moreover, relative to low GHET1 expression group, a poorer overall survival and relapse-free survival time existed in patients expressing high GHET1 expression (log-rank, P < 0.001). Multivariable analysis illustrated that GHET1 levels could be an independent index for the prognosis of patients diagnosed with esophageal cancer (P < 0.001, HR = 3.659, 95%CI: 2.208-6.061). Furthermore, GHET1 was found to bind directly with miR-105-3p, displaying an inverse correlation (r = -0.3790，P < 0.001). Experimental biological studies revealed silencing GHET1 could impede cell growth through the modulation of miR-105-3p (P < 0.001), which was rescued via transfecting miR-105-3p inhibitor in esophageal cancer.</p><p><strong>Conclusion: </strong>GHET1 emerges as a promising prognostic biomarker and tumor promoter in esophageal cancer, functioning through the modulation of miR-105-3p.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"13-23"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Molecular Mechanisms of N-Nitrosodimethylamine-Induced Colorectal Cancer: A Network Toxicology and Molecular Docking Analysis.","authors":"Jinyi Zhou, Dongyang He, Junzuo Lin, Hui Yao, Zhengfei Zhao","doi":"10.1615/JEnvironPatholToxicolOncol.2026062549","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2026062549","url":null,"abstract":"<p><strong>Background: </strong>N-nitrosodimethylamine (NDMA), a prevalent environmental contaminant found in food, water, and pharmaceuticals, is a recognized carcinogen strongly associated with colorectal cancer (CRC). However, the precise molecular mechanisms underlying NDMA-induced colorectal carcinogenesis remain incompletely understood. This study aimed to systematically investigate the molecular interactions between NDMA and CRC-related proteins to uncover potential mechanisms and therapeutic targets.</p><p><strong>Methods: </strong>We employed an integrated computational approach combining network toxicology and molecular docking. NDMA targets were identified using ChEMBL, STITCH, SwissTargetPrediction, and PharmMapper databases. CRC-associated genes were retrieved from GeneCards, OMIM, and TTD databases. Protein-protein interaction networks were constructed using STRING and analyzed with Cytoscape. Hub genes were identified through centrality analysis, validated using TCGA expression data, and subjected to molecular docking with AutoDock Vina.</p><p><strong>Results: </strong>We identified 370 NDMA targets and 1,575 CRC-related genes, with 91 overlapping genes representing potential mediators of NDMA-induced carcinogenesis. Enrichment analysis revealed significant involvement of xenobiotic response, MAPK signaling, and extracellular matrix remodeling pathways. Network analysis identified TP53, HSP90AB1, and HSP90AA1 as critical hub genes, all showing significant differential expression in CRC tissues (p < 0.05). Molecular docking revealed direct binding of NDMA to TP53 (-4.2 kcal/mol), HSP90AB1 (-4.6 kcal/mol), and HSP90AA1 (-3.8 kcal/mol), suggesting potential functional interference beyond genotoxic effects.</p><p><strong>Conclusion: </strong>This study elucidates multi-faceted mechanisms of NDMA-induced colorectal carcinogenesis, identifying TP53, HSP90AB1, and HSP90AA1 as key molecular targets. The convergence of network analysis, expression validation, and structural predictions provides a comprehensive framework for understanding NDMA toxicity and offers potential targets for preventing CRC in exposed populations.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 2","pages":"47-68"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics Unveils Key Genes in the MAPK Pathway in Colorectal Cancer and Predicts Prognosis, Immune Characteristics, and Potential Drugs.","authors":"Huixuan Hou, Long Zhang, Hualing Duan","doi":"10.1615/JEnvironPatholToxicolOncol.2025058410","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2025058410","url":null,"abstract":"<p><strong>Background: </strong>The Mitogen-Activated Protein Kinase (MAPK) signaling pathway is significant in clinical practice for its potential to impede tumor proliferation and migration and to enhance patient prognosis. Yet, the specific contributions of MAPK-related genes to the prognosis of colorectal cancer (CRC) are not clear.</p><p><strong>Methods: </strong>CRC data was retrieved from TCGA and GEO databases, with the MAPK pathway genes being identified from Kyoto Encyclopedia of Genes and Genomes (KEGG). A risk signature model for CRC associated with the MAPK pathway was formulated using regression analysis. The tumor immune microenvironment of high- and low-risk groups was assessed using single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms. We also looked into the potential differential response to immunotherapy by comparing immune checkpoints, immunophenoscore (IPS) scores, and Tumor Immune Dysfunction and Exclusion (TIDE) scores between the two groups. Moreover, the sensitivity to CRC treatment drugs in high- and low-risk groups was probed by forecasting drug IC50 values with the pRRophetic R package.</p><p><strong>Results: </strong>A risk model was established using eight distinct genes (CDC42, CACNA1D, EREG, TRAF2, MAPKAPK3, DDIT3, NGF, TGFB2) identified from the differential expression of MAPK-related genes. The analysis highlighted that patients in the high-risk group had a higher degree of immune cell infiltration but were less sensitive to immunotherapy (indicated by higher TIDE and lower IPS scores). Drug sensitivity predictions suggested that the high-risk group, despite their poor immunotherapy response, had an increased sensitivity to drugs such as Pazopanib, WH-4-023, and WZ-1-84.</p><p><strong>Conclusion: </strong>To encapsulate our findings, we have determined eight MAPK pathway-associated CRC prognostic biomarkers and developed a prognostic model accordingly. This model has proven effective in stratifying the risk levels among CRC patients.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"45 1","pages":"85-101"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}