{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T21:53:34Z","timestamp":1757627614802,"version":"3.44.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Photodynamic therapy (PDT) is an innovative non-invasive therapy for human cancer treatment. The significance of apoptosis-related genes (ARGs) in the prognosis of bladder cancer (BLCA) has gradually emerged. Therefore, this study aims to investigate the prognostic significance and pathogenesis of PDT related genes (PDTRGs)-ARGs in BLCA cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on the BLCA data in TCGA, PDTRGs-ARGs with prognostic value in BLCA patients were screened. Subsequently, the prognostic value and diagnostic performance of all candidate genes were evaluated by univariate Cox regression analysis and ROC curves. Then, GSEA, GSVA and immune microenvironment analysis were conducted based on candidate genes. Finally, the molecular mechanisms of key candidate genes in BLCA patients were initially explored by qRT-PCR, CCK-8 analysis, Transwell Assay and Western Blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 5 ARGs-PDTRGs (EMP1, FGFR1, PLPPR4, JUN, TNFRSF25) were screened as prognostic biomarkers for BLCA. Survival analysis revealed significant differences in overall survival of the five prognostic biomarkers in the high\/low expression groups. ROC curve analysis revealed that the five prognostic biomarkers had strong prognostic predictive ability. QRT-PCR proved that the expression of EMP1, FGFR1, PLPPR4 and JUN was obviously reduced, while TNFRSF25 was markedly increased in BLCA tissue samples and cell lines. The following research confirmed that FGFR1 inhibited the biological process of T24 cells by activating cGMP-PKG pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Five ARGs-PDTRGs (EMP1, FGFR1, PLPPR4, JUN, TNFRSF25) were screened as prognostic biomarkers for BLCA. Among them, FGFR1 inhibits the biological process of T24 cells via activating cGMP-PKG pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1578695","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:18:11Z","timestamp":1757477891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic value and molecular mechanism of photodynamic therapy and apoptosis related gene FGFR1 in bladder cancer"],"prefix":"10.3389","volume":"15","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangzhou","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhunan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e076743","DOI":"10.1136\/bmj-2023-076743","article-title":"Advances in diagnosis and treatment of bladder cancer","volume":"384","author":"Lopez-Beltran","year":"2024","journal-title":"Bmj"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.3390\/ijms25031557","article-title":"Mini-review: current bladder cancer treatment-the need for improvement","volume":"25","author":"Gill","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3390\/ijerph21070954","article-title":"Risk factors associated with urothelial bladder cancer","volume":"21","author":"Alouini","year":"2024","journal-title":"Int J Environ Res Public Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1481296","article-title":"Bladder cancer immune-related markers: diagnosis, surveillance, and prognosis","volume":"15","author":"Yang","year":"2024","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31020079","article-title":"Bcg and alternative therapies to bcg therapy for non-muscle-invasive bladder cancer","volume":"31","author":"Lidagoster","year":"2024","journal-title":"Curr Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1607","article-title":"Cd164 promotes tumor progression and predicts the poor prognosis of bladder cancer","volume":"7","author":"Zhang","year":"2018","journal-title":"Cancer Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116312","article-title":"Potential molecular biomarkers for the diagnosis and prognosis of bladder cancer","volume":"173","author":"Fan","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B8","doi-asserted-by":"publisher","first-page":"11325","DOI":"10.3390\/ijms252011325","article-title":"Photodynamic therapy: past, current, and future","volume":"25","author":"Aebisher","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"12069","DOI":"10.3390\/ijms252212069","article-title":"Determinants of photodynamic therapy resistance in cancer cells","volume":"25","author":"D\u0105browska","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"731","DOI":"10.3390\/molecules27030731","article-title":"Advances in management of bladder cancer-the role of photodynamic therapy","volume":"27","author":"Kubrak","year":"2022","journal-title":"Molecules"},{"key":"B11","doi-asserted-by":"publisher","first-page":"960","DOI":"10.3390\/ijms25020960","article-title":"Photodynamic therapy: current trends and potential future role in the treatment of bladder cancer","volume":"25","author":"Kochergin","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.3390\/cancers16132299","article-title":"Photodynamic diagnosis and therapy in non-muscle-invasive bladder cancer","volume":"16","author":"Kurabayashi","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1335920","article-title":"The impact of photodynamic therapy on immune system in cancer-an update","volume":"15","author":"Dudzik","year":"2024","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.30173","article-title":"Review of cancer cell resistance mechanisms to apoptosis and actual targeted therapies","volume":"123","author":"Kulbay","year":"2022","journal-title":"J Cell Biochem"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1590\/1519-6984.228437","article-title":"Apoptosis (Programmed cell death) and its signals-a review","volume":"81","author":"Obeng","year":"2021","journal-title":"Braz J Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.18591","article-title":"Identification and validation of apoptosis-related genes in acute myocardial infarction based on integrated bioinformatics methods","volume":"12","author":"Zhu","year":"2024","journal-title":"PeerJ"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3646","article-title":"Necrotizing apoptosis-related genes prognosis and treatment effect analysis of osteosarcoma in children","volume":"26","author":"Chen","year":"2024","journal-title":"J Gene Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1038\/s41598-024-54673-x","article-title":"Novel molecular hepatocellular carcinoma subtypes and riskscore utilizing apoptosis-related genes","volume":"14","author":"Zhang","year":"2024","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12920-023-01525-8","article-title":"Apoptosis related genes mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide immunotherapy in bladder cancer","volume":"16","author":"Zhou","year":"2023","journal-title":"BMC Med Genomics"},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","DOI":"10.1214\/16-aoas920","article-title":"Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression","volume":"10","author":"Phipson","year":"2016","journal-title":"Ann Appl Stat"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","article-title":"Clusterprofiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v039.i05","article-title":"Regularization paths for cox\u2019s proportional hazards model via coordinate descent","volume":"39","author":"Simon","year":"2011","journal-title":"J Stat Softw"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v106.i01","article-title":"Elastic net regularization paths for all generalized linear models","volume":"106","author":"Tay","year":"2023","journal-title":"J Stat Softw"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77","article-title":"Proc: an open-source package for R and S+ to analyze and compare roc curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinf"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102530","article-title":"Role of fgfr3 in bladder cancer: treatment landscape and future challenges","volume":"115","author":"Ascione","year":"2023","journal-title":"Cancer Treat Rev"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12602","article-title":"Fgfr3 alterations in bladder cancer: sensitivity and resistance to targeted therapies","volume":"44","author":"Noeraparast","year":"2024","journal-title":"Cancer Commun (Lond)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.91874","article-title":"Fgl2 as a predictive biomarker for prognosis and immunotherapy in bladder cancer","volume":"21","author":"Huang","year":"2024","journal-title":"Int J Med Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41572-023-00468-9","article-title":"Bladder cancer","volume":"9","author":"Dyrskj\u00f8t","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/php.13726","article-title":"Photodynamic therapy for bladder cancers, a focused review(\u2020)","volume":"99","author":"Rahman","year":"2023","journal-title":"Photochem Photobiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7150\/thno.67300","article-title":"Recent advances in nanomedicines for photodynamic therapy (Pdt)-driven cancer immunotherapy","volume":"12","author":"Ji","year":"2022","journal-title":"Theranostics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12894-023-01331-5","article-title":"Establishment of prognostic model of bladder cancer based on apoptosis-related genes, in which P4hb promotes blca progression","volume":"23","author":"Zou","year":"2023","journal-title":"BMC Urol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"10482","DOI":"10.1038\/s41598-024-61302-0","article-title":"Predicting bladder cancer survival with high accuracy: insights from mapk pathway-related genes","volume":"14","author":"Cheng","year":"2024","journal-title":"Sci Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14878","article-title":"Therapeutic and prognostic implications of notch and mapk signaling in bladder cancer","volume":"112","author":"Schulz","year":"2021","journal-title":"Cancer Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155633","article-title":"Association of viral infection with bladder cancer: A systematic review and meta-analysis","volume":"264","author":"Motlaghzadeh","year":"2024","journal-title":"Pathol Res Pract"},{"key":"B36","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1007\/s12672-024-01575-z","article-title":"Predicting survival in bladder cancer with a novel apoptotic gene-related prognostic model","volume":"15","author":"Song","year":"2024","journal-title":"Discov Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e11343","article-title":"A novel 17 apoptosis-related genes signature could predict overall survival for bladder cancer and its associations with immune infiltration","volume":"8","author":"Wang","year":"2022","journal-title":"Heliyon"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.14440\/bladder.2023.852","article-title":"Single-cell analyses emp1 as a marker of the ratio of M1\/M2 macrophages is associated with emt, immune infiltration, and prognosis in bladder cancer","volume":"10","author":"Li","year":"2023","journal-title":"Bladder (San Franc)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"10496","DOI":"10.3390\/ijms231810496","article-title":"Ttyh3 modulates bladder cancer proliferation and metastasis via fgfr1\/H-ras\/a-raf\/mek\/erk pathway","volume":"23","author":"Biswas","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17899","article-title":"Plppr4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via mtor signaling","volume":"27","author":"Li","year":"2023","journal-title":"J Cell Mol Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-24-669","article-title":"Dephosphorylation-related signature predicts the prognosis of papillary renal cell carcinoma","volume":"13","author":"Feng","year":"2024","journal-title":"Trans Cancer Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108242","article-title":"Jun mediates glucocorticoid resistance by stabilizing hif1a in T cell acute lymphoblastic leukemia","volume":"26","author":"Zhang","year":"2023","journal-title":"iScience"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.Mcr-22-0695","article-title":"Targeting C-jun is a potential therapy for luminal breast cancer bone metastasis","volume":"21","author":"Han","year":"2023","journal-title":"Mol Cancer Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-008810","article-title":"Targeting tnfrsf25 by agonistic antibodies and multimeric tl1a proteins co-stimulated cd8(+) T cells and inhibited tumor growth","volume":"12","author":"Lyu","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.Mcr-23-0955","article-title":"Fgfr1 signaling facilitates obesity-driven pulmonary outgrowth in metastatic breast cancer","volume":"22","author":"Kulkoyluoglu Cotul","year":"2024","journal-title":"Mol Cancer Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46110783","article-title":"Pharmacological and biological targeting of fgfr1 in cancer","volume":"46","author":"Fan","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155612","article-title":"Targeting fgfr1 by \u03b2,\u03b2-dimethylacrylalkannin suppresses the proliferation of colorectal cancer in cellular and xenograft models","volume":"129","author":"Zhao","year":"2024","journal-title":"Phytomedicine"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217694","article-title":"Metformin inhibits the progression of castration-resistant prostate cancer by regulating pde6d induced purine metabolic alternation and cgmp\/pkg pathway activation","volume":"622","author":"Cai","year":"2025","journal-title":"Cancer Lett"},{"key":"B49","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1007\/s12672-025-02512-4","article-title":"Pttg1 promotes M2 macrophage polarization via the cgmp-pkg signaling pathway and facilitates emt progression in human epithelial ovarian cancer cells","volume":"16","author":"Tian","year":"2025","journal-title":"Discov Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2023.2267301","article-title":"Knowledge-map analysis of bladder cancer immunotherapy","volume":"19","author":"Lv","year":"2023","journal-title":"Hum Vaccin Immunother"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22603","article-title":"Insights on recent innovations in bladder cancer immunotherapy","volume":"130","author":"Abd El-Salam","year":"2022","journal-title":"Cancer Cytopathol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1235884","article-title":"The bladder cancer immune micro-environment in the context of response to immune checkpoint inhibition","volume":"14","author":"van Dorp","year":"2023","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1016\/j.cell.2020.05.017","article-title":"Intratumoral cd4(+) T cells mediate anti-tumor cytotoxicity in human bladder cancer","volume":"181","author":"Oh","year":"2020","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.844142","article-title":"Immunotherapy: reshape the tumor immune microenvironment","volume":"13","author":"Lv","year":"2022","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-04860-1","article-title":"Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer","volume":"22","author":"Yuan","year":"2024","journal-title":"J Transl Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41573-022-00520-5","article-title":"Macrophages as tools and targets in cancer therapy","volume":"21","author":"Mantovani","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B57","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s12943-020-01238-x","article-title":"Natural killer cells in cancer biology and therapy","volume":"19","author":"Wu","year":"2020","journal-title":"Mol Cancer"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2024.2378520","article-title":"Human nk cells and cancer","volume":"13","author":"Cantoni","year":"2024","journal-title":"Oncoimmunology"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-020-01634-0","article-title":"Photodynamic therapy: apoptosis, paraptosis and beyond","volume":"25","author":"Kessel","year":"2020","journal-title":"Apoptosis"},{"key":"B60","doi-asserted-by":"publisher","first-page":"13129","DOI":"10.1038\/s41598-025-97667-z","article-title":"Pdt-regulated immune gene prognostic model reveals tumor microenvironment in colorectal cancer liver metastases","volume":"15","author":"Xu","year":"2025","journal-title":"Sci Rep"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2020.101809","article-title":"Deep proteome profiling of sw837 cells treated by photodynamic therapy (Pdt) reveals the underlying mechanisms of metronomic and acute pdts","volume":"31","author":"Gao","year":"2020","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S467512","article-title":"Ros-responsive nanoprobes for bimodal imaging-guided cancer targeted combinatorial therapy","volume":"19","author":"Jiang","year":"2024","journal-title":"Int J Nanomed"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117509","article-title":"Sodium bicarbonate potentiates the antitumor effects of olaparib in ovarian cancer via cgmp\/pkg-mediated ros scavenging and M1 macrophage transformation","volume":"180","author":"Li","year":"2024","journal-title":"BioMed Pharmacother"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1578695\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:18:13Z","timestamp":1757477893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1578695\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":63,"alternative-id":["10.3389\/fonc.2025.1578695"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1578695","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]},"article-number":"1578695"}}