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Early detection is hindered by limited reliable biomarkers and cost-effective screening methods. Phage biosensors provide an approach for early diagnosis using non-invasive liquid biopsies. This study reports bifunctional chemical-and-phage biosensor results for classifying metastatic urological cancers from urine. Using a dye-sensitized phage library, metastasis-related binders were selected and tested against controls. After selection rounds, the top phage candidate performed classification, and a non-fluorescent phenoxazine dye chemical sensor provided complementary discrimination. Statistical tests showed significance between metastatic and non-metastatic cancer (p = 0.0002), with sensitivity 70% and specificity 79% for the phage method, and p \u003C 0.0001 with sensitivity 71% and specificity 75% for the chemical sensor. 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The chemical sensor also showed significance (p \u003C 0.0001) with sensitivity 71% and specificity 75%.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332092,1790627840,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","life  \nArticle  \nPhage Biosensor for the Classification of Metastatic Urological Cancers from Urine  \nVilhelmiina Juusti 1,2, *, Antti Rannikko 3, Anu Laurila 4, Maria Sundvall 4,5, Pekka Hänninen 1 and Janne Kulpakko 2  \nCitation: Juusti, V.; Rannikko, A.; Laurila, A.; Sundvall, M.; Hänninen, P.; Kulpakko, J. Phage Biosensor for the Classification of Metastatic Urological Cancers from Urine. Life 2024, 14, 600. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/life14050600](10.3390/life14050600)  \nAcademic Editor: Li Gao  \nReceived: 28 March 2024  \nRevised: 2 May 2024  \nAccepted: 6 May 2024  \nPublished: 8 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Laboratory of Biophysics and Medicity Research Laboratories, Institute of Biomedicine, Faculty of Medicine, University of Turku, Tykistökatu 6A, 20520 Turku, Finland  \n2 Aqsens Health Ltd., Itäinen Pitkäkatu 4B, 20520 Turku, Finland  \n3 Department of Urology, Helsinki University, Helsinki University Hospital, 00280 Helsinki, Finland  \n4 Department of Oncology, Turku University Hospital, PL52, 20521 Turku, Finland  \n5 Cancer Research Unit, Institute of Biomedicine, FICAN West Cancer Center Laboratory, University of Turku, Turku University Hospital, Kiinamyllynkatu 10, 20520 Turku, Finland  \n* [Correspondence: hmvleh@utu.fi](Correspondence: hmvleh@utu.fi)  \nAbstract: Most of the annual 10 million cancer-related deaths are caused by metastatic disease. Survival rates for cancer are strongly dependent on the type of cancer and its stage at detection. Early detection remains a challenge due to the lack of reliable biomarkers and cost-efficient screening methods. Phage biosensors can offer a solution for early detection using non-invasive liquid biopsies. Here, we report the first results of the bifunctional phage biosensor to detect metastatic urological cancers from urine. A dye-sensitized phage library was used to select metastasis-related phage binders. After selection rounds, the most promising phage candidate was used to classify metastatic cancer from controls. Additionally, we applied one chemical sensor (phenoxazine non-fluorescent dye) to classify cancer from urine. A statistical significance (p = 0.0002) was observed between metastatic and non-metastatic cancer, with sensitivity of 70% and specificity of 79% . Furthermore, the chemical sensor demonstrated significance in detecting cancer (p \u003C 0.0001) with a sensitivity of 71% and a specificity of 75% . Our data suggest a new promising field for urine biomarker research, and further evaluation with prospectively collected samples is ongoing. In conclusion, we report, for the first time, the potential of a chemical-and phage-based biosensor method to detect metastatic cancer using urine.  \nKeywords: phage; biosensor; phage biosensor; chemical sensor; metastatic cancer; urological cancer; liquid biopsy; urine; liquid crystal  \n1. Introduction  \nCancer is a notable health challenge of the 21st century. Despite vast efforts in research, detection, and treatment, it was still among the leading causes of death in 2022 [1] . Most cancer-related morbidity and mortality is caused by metastases [2,3] . The formation of metastases is a process in which a malignant cell invades and migrates from the primary origin to surrounding tissue or distant secondary organs and establishes a macroscopic secondary focus, commonly known as metastasis. Metastasis formation is regulated by a complex interplay of genetic and epigenetic alterations in the cell, shaping cell morphology and phenotype [4,5] . Cells can metastasize even before the primary tumors are detectable with conventional detection methods [3], caus","cbCainh48TjbyhFh","https://ap.wps.com/l/cbCainh48TjbyhFh","pdf",2025518,14,"English","# Abstract\n# Introduction\n## Metastasis and detection challenges\n## Biomarker limitations and liquid biopsy potential","[{\"question\":\"Why is early detection of metastatic cancer challenging?\",\"answer\":\"Early detection is difficult because clinically reliable biomarkers are limited and cost-efficient screening methods are lacking. The study highlights the need for dependable markers for metastatic disease.\"},{\"question\":\"How does the proposed biosensor classify metastatic urological cancers?\",\"answer\":\"The approach combines a dye-sensitized phage library to select metastasis-related phage binders and a chemical sensor using a non-fluorescent phenoxazine dye. Selected components are then used to classify urine samples from controls versus metastatic cases.\"},{\"question\":\"What performance metrics were reported for phage and chemical sensing?\",\"answer\":\"For metastatic versus non-metastatic classification, the phage biosensor showed significance (p = 0.0002) with sensitivity 70% and specificity 79%. The chemical sensor also showed significance (p \\u003c 0.0001) with sensitivity 71% and specificity 75%.\"}]","Phage Biosensor for the Classification of Metastatic Urological Cancers from Urine | PDF",1789996710,35]