Cytojournal最新文献

{"title":"Radiomics meets pathology: Building the bridge for precision oncology.","authors":"Vittorio Patanè, Maria Chiara Brunese, Luca Marinelli, Erika Martinelli, Valerio Nardone, Renato Franco, Salvatore Cappabianca, Alfonso Reginelli","doi":"10.25259/Cytojournal_170_2025","DOIUrl":"10.25259/Cytojournal_170_2025","url":null,"abstract":"","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"39"},"PeriodicalIF":2.2,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics identification of forkhead box O3 and the proto-oncogene tyrosine-protein kinase receptor RET as aging-associated biomarkers linked to immune cell infiltration in Parkinson's disease.","authors":"Haoran Zheng, Ao Guan, Xiang Li, Xiang Zhang, Lan Zheng, Yanxin Zhao","doi":"10.25259/Cytojournal_127_2025","DOIUrl":"10.25259/Cytojournal_127_2025","url":null,"abstract":"<p><strong>Objectives: </strong>Parkinson's disease (PD), the second most prevalent neurodegenerative disease, is closely linked to aging and immune system dysfunction. This study aims to explore potential aging-related biomarkers of PD and examine their diagnostic value, in addition to their relationship with immune cell infiltration, to identify novel therapeutic targets.</p><p><strong>Methods: </strong>Gene expression profiles from the gene expression omnibus (GEO) database (GSE20163, GSE20164, and GSE8397) were analyzed. Aging-related genes associated with PD were screened using weighted gene co-expression network analysis. Subsequent functional enrichment analysis, protein‒protein interaction (PPI) network mapping, and least absolute shrinkage and selection operator regression were used to identify key biomarker candidates. A receiver operating characteristic (ROC) curve analysis was applied to evaluate diagnostic efficacy. Immune cell infiltration was assessed through Spearman correlation analysis, and the expression of key biomarkers was validated in both cellular and animal PD models.</p><p><strong>Results: </strong>Eighteen aging-related genes were identified through a PPI network analysis. Seven genes, including forkhead box O3 (FOXO3) and the proto-oncogene tyrosine-protein kinase receptor rearranged during transfection (RET), showed potential as diagnostic biomarkers for PD. Gene set enrichment analysis revealed that these biomarkers correlated with immune cell infiltration patterns in PD patients. The ROC curve analysis indicated high diagnostic accuracy for these genes across multiple datasets (area under the curve = 96.3158). <i>In vivo</i> and <i>in vitro</i> validation confirmed significant changes in the expression of RET and FOXO3 in PD samples, highlighting their relevance as biomarkers.</p><p><strong>Conclusion: </strong>Our findings suggest that RET and FOXO3 are promising aging-related biomarkers for PD, potentially providing new insights into the early diagnosis and targeted treatment of PD. These biomarkers also reflect the complex interplay between aging, immunity, and PD pathogenesis.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"38"},"PeriodicalIF":2.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vibrational spectroscopy in cellular and molecular pathology: From optical signatures to diagnostic insight.","authors":"Charlotte Delrue, Sander De Bruyne, Marijn M Speeckaert","doi":"10.25259/Cytojournal_200_2025","DOIUrl":"10.25259/Cytojournal_200_2025","url":null,"abstract":"","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"37"},"PeriodicalIF":2.2,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myxoid spindle cell lipoma of the ileum: Clinicopathological features and diagnostic insights.","authors":"Ruirui Fan, Jie Gao","doi":"10.25259/Cytojournal_27_2026","DOIUrl":"10.25259/Cytojournal_27_2026","url":null,"abstract":"<p><strong>Objective: </strong>This study analyzes a rare myxoid spindle cell lipoma (SCL) around the ileum. It aims to systematically summarize the clinicopathological features of this tumor at an atypical location. This will improve understanding of this rare condition.</p><p><strong>Material and methods: </strong>We conducted a detailed study of SCL around the ileum. This mass was incidentally found in a right hemicolectomy specimen. The analysis integrated multiple methods. These included histomorphological observation, immunohistochemical staining, and molecular testing.</p><p><strong>Results: </strong>The tumor showed a typical myxoid stromal background. It contained spindle cells and scattered mature adipocytes. The characteristic thick collagen bundles commonly seen in classic SCL were absent. A diagnosis of myxoid SCL was confirmed based on the following features: CD34-positive spindle cells, loss of retinoblastoma protein 1expression, a low Ki-67 index, and the absence of MDM2 amplification by both IHC and fluorescence in situ hybridization. This profile effectively excludes malignant differential diagnoses, such as liposarcoma.</p><p><strong>Conclusion: </strong>Myxoid SCL around the ileum is extremely rare. Its diagnosis relies on recognizing its characteristic morphological spectrum. Immunohistochemistry and molecular testing are essential to exclude malignant tumors. A comprehensive understanding of its unique presentation at atypical sites is crucial. This is important for achieving accurate diagnosis and preventing inappropriate treatment.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"36"},"PeriodicalIF":2.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fat mass and obesity-associated gene overexpression ameliorates endothelial dysfunction after myocardial infarction by mediating N6-methyladenosine modification of ATP-binding cassette subfamily F member 1.","authors":"Huichao Pan, Xunlong Xu, Yamei Yu, Zhaohui Qiu, Yafeng Zhou","doi":"10.25259/Cytojournal_97_2025","DOIUrl":"10.25259/Cytojournal_97_2025","url":null,"abstract":"<p><strong>Objectives: </strong>Myocardial infarction (MI) is linked to high mortality, which highlights the need for early diagnosis and intervention to prevent heart failure. N6-methyladenosine (m6A) methylation of ribonucleic acid (RNA) influences endothelial dysfunction and MI. Here, the effects and associated mechanisms of fat mass and obesity-associated gene (FTO) on vascular endothelial cell (EC) function, as well as myocardial damage in mice following MI were investigated.</p><p><strong>Material and methods: </strong>A human umbilical vein EC (HUVEC) model of oxygen-glucose deprivation (OGD) as well as a mouse MI model were used to detect MI-induced endothelial and myocardial damage. EC function was examined using cell-counting-kit-8, wound healing, migration, and tube formation assays. Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were utilized to analyze the m6A modifications and RNA expression patterns in control and FTO-overexpressing ECs following OGD. FTO and ATP-binding cassette subfamily F member 1 (ABCF1) levels were evaluated using western blotting. The relationship between FTO and ABCF1 was determined using RNA immunoprecipitation-quantitative polymerase chain reaction (RIPqPCR), MeRIP-qPCR, and RNA stability assays. Echocardiography and Masson's trichrome and hematoxylineosin staining were used to measure myocardial injury.</p><p><strong>Results: </strong>FTO expression was reduced in infarcted myocardial tissue and OGD-induced HUVECs (<i>P</i> < 0.01). Functionally, FTO overexpression improved the impaired function of OGD-treated HUVECs and restored myocardial function in MI mice (<i>P</i> < 0.01). Mechanistically, FTO reduced m6A methylation of ABCF1 mRNA and raised ABCF1 levels in OGD-treated HUVECs (<i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>Taken together, our study revealed that FTO overexpression restored OGD-induced endothelial dysfunction and myocardial pathological injury after MI. FTO increased ABCF1 expression in OGD-treated HUVECs through an m6A-dependent mechanism. These findings offer new insights into mitigating EC dysfunction and myocardial injury after MI.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"35"},"PeriodicalIF":2.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive detection of endometrial cancer through exfoliated cervical cell gene methylation signatures: Evaluation of <i>CELF4/GALR1/ZNF486</i> methylation biomarkers.","authors":"Xing Fan, Saiping Mao, Yingxia Ou, Fang Yu, Xiaoli Wang, Rong Wang","doi":"10.25259/Cytojournal_135_2025","DOIUrl":"10.25259/Cytojournal_135_2025","url":null,"abstract":"<p><strong>Objective: </strong>The current non-invasive screening methods for endometrial cancer (EC), such as transvaginal ultrasound (TVUS), lack sufficient specificity, leading to unnecessary invasive diagnostic procedures. The detection of cancer-specific deoxyribonucleic acid (DNA) methylation alterations in cervical cytology samples presents a promising, minimally invasive alternative. This study aimed to evaluate the diagnostic potential of novel DNA methylation biomarkers (CUGBP Elav-like family member 4 methylation [<i>CELF4^m</i> ], Galanin receptor 1 methylation [<i>GALR1^m</i> ], Zinc finger protein 486 methylation [<i>ZNF486^m</i> ]) in cervical exfoliated cells for EC screening.</p><p><strong>Material and methods: </strong>This case-control study enrolled patients scheduled for diagnostic or surgical curettage at the hospital from September 2024 to June 2025. A total of 104 women underwent endometrial evaluation (32 type I EC, 3 type II EC, 61 benign lesions [BL], 8 atypical hyperplasia). Quantitative methylation-specific polymerase chain reaction assessed biomarker performance against histopathological diagnosis.</p><p><strong>Results: </strong>All three markers (<i>CELF4^m, GALR1^m, ZNF486^m</i> ) showed significant differential ΔCp values between BL and EC groups (all <i>P</i> < 0.01), with moderate diagnostic accuracy (area under the ROC curve [AUCs]: 0.654-0.704). The single-marker <i>GALR1^m</i> outperformed endometrial thickness (ET) measured by TVUS in specificity (60.9% vs. 27.5%, <i>P</i> < 0.001) while maintaining comparable sensitivity (80.0% vs. 74.3%, <i>P</i> = 0.527). A two-marker panel (<i>GALR1^m</i> /<i>ZNF486^m</i> , Model 1) achieved sensitivity (97.1% [95% confidence interval [CI]: 91.6-100%]) with modest specificity (49.3% [95% CI: 37.5-61.1%]). Among three-gene models, Model 3 demonstrated the highest overall performance (AUC: 0.733 [95% CI: 0.657-0.808]; sensitivity: 91.4% [95% CI: 82.1-100%]), whereas Model 4 balanced sensitivity (80.0% [95% CI: 66.7-93.3%]) and improved specificity (63.8% [95% CI: 52.4-75.1%]).</p><p><strong>Conclusion: </strong>DNA methylation signatures in cervical cells show superior diagnostic accuracy to conventional ET measured by TVUS, particularly through multi-marker panels. This non-invasive approach represents a promising EC screening strategy.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"34"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical correlates of human papillomavirus infection: A study of 7,601 women attending a tertiary referral center in Greece.","authors":"Nikiforos Stamoulis, Evgenia Charikleia Lazari, Charalampos Theofanakis, Andreas C Lazaris, Periklis Panagopoulos, Georgia Eleni Thomopoulou","doi":"10.25259/Cytojournal_153_2025","DOIUrl":"10.25259/Cytojournal_153_2025","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to analyze the prevalence, genotype distribution, and infection burden of human papillomavirus (HPV) as well as their association with cytological findings, among 7,601 women attending a tertiary referral center in Athens, Greece.</p><p><strong>Materials and methods: </strong>This retrospective, single-center cross-sectional study analyzed cervical samples from women attending a specific institution (2019-2024) that underwent polymerase chain reaction-based HPV genotyping, while cytological findings were classified according to the Bethesda system. Statistical analyses assessed the relationships between HPV types, infection burden, cytological outcomes, and age groups.</p><p><strong>Results: </strong>Overall HPV prevalence was 31%, including 18.4% single and 12.6% multiple infections. The most frequent HPV genotypes detected were HPV-42, HPV-51, HPV-16, HPV-53, and HPV-54. Multiple infections were more common in younger women, while single infections predominated with increasing age. Cytological results showed 82.3% normal, 15.9% low-grade squamous intraepithelial lesions (LSILs), 1.3% atypical squamous cells of undetermined significance (ASC-US), and 0.5% high-grade squamous intraepithelial lesions (HSILs). HPV types 16, 18, 31, 33, 42, and 51 were strongly associated with LSIL and/or HSIL. Women with multiple HPV infections had higher odds of ASC-US and LSIL compared to those with single infections; however, the opposite pattern was observed for HSIL. Age was inversely associated with ASC-US and LSIL but not with HSIL.</p><p><strong>Conclusion: </strong>These findings highlight the importance of HPV genotype and infection burden in cervical disease risk in this patient cohort and underscore the need for targeted screening and vaccination strategies tailored to the local epidemiology.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"30"},"PeriodicalIF":2.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148254096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-aminobutyric acid affects the tumor microenvironment and angiogenesis, promoting breast cancer progression.","authors":"Hui Wang, Jingxia Bao, Danfeng Lin","doi":"10.25259/Cytojournal_143_2025","DOIUrl":"10.25259/Cytojournal_143_2025","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer (BC) is one of the most common malignant tumors among women. Gamma-aminobutyric acid (GABA) is abnormally expressed in various cancers, but its effect on BC remains unclear. This study aims to explore the expression changes of glutamic acid decarboxylase 1 (GAD1) in BC and its mechanism of promoting tumor occurrence and development by regulating GABA synthesis.</p><p><strong>Material and methods: </strong>GAD1 expression and GABA levels in BC cells (MDA-MB-231) and normal breast epithelial cells (MCF-10A) were measured. GAD1 overexpression and knockdown cell lines were constructed to evaluate the changes in GABA levels and their effects on cell proliferation and invasion ability. Macrophage M2 polarization and protumor factor levels were analyzed by coculturing tumor cells with macrophages. Cell activity was detected by coculturing with CD8⁺ T cells, and tumor immune responses were examined by immunofluorescence and cytokine detection. <i>In vitro</i> tube formation was used to simulate angiogenesis, and angiogenesis ability was detected. Western blot was used to analyze the expression of vascular endothelial cell markers, and calcium-tracer dyes were used to detect calcium ion (Ca²⁺) influx in endothelial cells.</p><p><strong>Results: </strong>GAD1 expression and GABA level in MDA-MB-231 cells were significantly higher than those in normal cells (<i>P</i> <0.01). GAD1 overexpression enhanced cell proliferation, invasion, and migration abilities and simultaneously promoted macrophage polarization to M2, releasing protumor factors interleukin-10 and transforming growth factor-beta and inhibiting the antitumor effect of M1-type macrophages (<i>P</i> <0.05). GAD1 inhibition had the opposite effect (<i>P</i> <0.01). GAD1 overexpression also suppressed the activity of CD8⁺ T cells; decreased the expression of programmed death-1 in CD8⁺T cells and the levels of interferon-gamma, perforin, and granzyme B; weakened the immune response; and promoted tumor angiogenesis (<i>P</i> <0.05). The number of <i>in vitro</i> vascular lumen formation increased, the expression of vascular markers rose, and Ca²⁺ influx was enhanced (<i>P</i> <0.01). Reverse operation demonstrated that GABA promoted the initiation and advancement of BC by regulating the immune microenvironment and angiogenesis (<i>P</i> <0.05).</p><p><strong>Conclusion: </strong>GAD1 is highly expressed in BC. Increasing GABA synthesis promotes tumor cell proliferation and metastasis, regulates the immune microenvironment toward immunosuppression, and enhances tumor angiogenesis. This work reveals the crucial role of the GAD1-GABA pathway in BC and provides a potential therapeutic target for this disease.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"31"},"PeriodicalIF":2.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148254053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of junctional adhesion molecule 3 and paired box gene 1 methylation, cytology, E6/E7 messenger RNA, and high-risk human papillomavirus testing for detecting precancerous cervical lesions.","authors":"Shan Luo, Chunlin Tao, Fengmian Wang, Tingyan Shi, Rong Zhang","doi":"10.25259/Cytojournal_239_2024","DOIUrl":"10.25259/Cytojournal_239_2024","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluated paired box gene 1 (<i>PAX1</i>) and junctional adhesion molecule 3 (<i>JAM3</i>) methylation as biomarkers for detecting cervical precancerous lesions, comparing their performance with cytology, E6/E7 messenger RNA (mRNA) testing, and high-risk human papillomavirus (hrHPV) detection.</p><p><strong>Material and methods: </strong>This retrospective study included 288 patients with abnormal human papillomavirus (HPV)-DNA or cytological findings warranting colposcopy who were enrolled between February 2023 and February 2024. Demographic data, cytology, HPV-DNA, E6/E7 mRNA, and <i>PAX1/JAM3</i> methylation results were analyzed. Optimal methylation thresholds were identified using Youden's index.</p><p><strong>Results: </strong>Methylation rates of <i>PAX1</i> and <i>JAM3</i> correlated with lesion severity: The combined positive rate of <i>PAX1</i> and <i>JAM3</i> methylation (positive for either marker) increased progressively from normal tissues (11.6%) to low-grade squamous intraepithelial lesion (LSIL) (27.8%), high-grade squamous intraepithelial lesion (HSIL) (79.2%), and cancer (100%). For HSIL + detection, <i>PAX1/JAM3</i> methylation showed high sensitivity (82.0%), specificity (83.3%), and an area under the curve (AUC) of 0.826. Comparatively, AUCs for cytology, HPV 16/18, hrHPV, and E6/E7 testing ranged from 0.578 to 0.768. Combining <i>PAX1/JAM3</i> with these methods improved diagnostic performance, with AUCs up to 0.831.</p><p><strong>Conclusion: </strong><i>PAX1</i> and <i>JAM3</i> methylation testing demonstrates robust diagnostic potential for cervical precancerous lesions and complements existing screening methods.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"33"},"PeriodicalIF":2.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148254089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combine immune checkpoint indoleamine 2,3-dioxygenase 1 knockdown with ferroptosis inducer Erastin/RSL3 accelerates colorectal cancer cell ferroptosis.","authors":"Fei Li, Taixi Xu, Yingpei Ling, Jiajia Xu, Xiwen Zhang, Shumei Sun","doi":"10.25259/Cytojournal_262_2024","DOIUrl":"10.25259/Cytojournal_262_2024","url":null,"abstract":"<p><strong>Objective: </strong>Colorectal cancer (CRC) is a malignancy known for its aggressive behavior and notable mortality burden. Indoleamine 2,3-dioxygenase 1 (IDO1), an immune checkpoint molecule, is markedly upregulated in CRC, and it has been implicated in the regulation of key components of the ferroptosis pathway. This study aimed to elucidate the regulatory interaction between IDO1 and ferroptosis and assess the potential therapeutic effect of combined IDO1 inhibition with ferroptosis inducers Erastin and RSL3 in CRC.</p><p><strong>Material and methods: </strong>Three CRC cell lines (CT26, MC38, and HT-29) and one normal colon epithelial cell line (NCM460) were treated with ferroptosis inducers to evaluate the changes in IDO1 expression through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. MC38 cells with stable IDO1 knockdown were generated through lentiviral transduction. The expressions of ferroptosis-related genes following IDO1 silencing were assessed through RT-qPCR and Western blot. The antitumor efficacy of combined IDO1 knockdown and Erastin/RSL3 treatment was evaluated through cell counting kit-8, Transwell migration, and wound-healing assays. Enzyme-linked immunosorbent assay was employed to quantify intracellular levels of glutathione (GSH) and malondialdehyde (MDA). Reactive oxygen species (ROS) levels were measured via flow cytometry, and ferrous ion (Fe²⁺)and nicotinamide adenine dinucleotide phosphate (NADPH) concentrations were determined through colorimetric analysis.</p><p><strong>Results: </strong>Treatment with Erastin and RSL3 upregulated IDO1 expression in CRC cells. Silencing of IDO1 in MC38 cells resulted in increased expressions of cyclooxygenase-2, acyl-CoA synthetase long chain family member 4, and NADPH oxidase 1, alongside decreased expression of GSH peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, and nuclear factor E2-related factor 2. The combination of IDO1 knockdown with Erastin/RSL3 treatment significantly reduced the proliferation, invasion, and migration of MC38 cells (<i>P</i> < 0.001). This combined treatment also elevated intracellular MDA, ROS, and Fe²⁺ levels while lowering GSH and NADPH levels.</p><p><strong>Conclusion: </strong>Combination therapy with IDO1 inhibitor and ferroptosis inducer may be an effective way to improve treatment efficacy in CRC.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"23 ","pages":"32"},"PeriodicalIF":2.2,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13260877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148254114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}