{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:57:27Z","timestamp":1790776647189,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Suez Canal University","award":["3\/2020"],"award-info":[{"award-number":["3\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) spectra were acquired from urine samples using direct application. Spectral processing and normalization were optimized using parameter grid searching. We assessed their technical variability through multivariate analysis and principal component analysis (PCA). We assessed 35 machine learning models on a training set (70%), and the performance was evaluated on a held-out test set (30%). A Regularized Random Forests (RRF) model achieved a 0.92 area under the receiver operating characteristic (AUROC) with 86% sensitivity and 77% specificity. In conclusion, our spectroscopic liquid biopsy approach provides a promising technique for the early identification of NMIBC with a less invasive examination.<\/jats:p>","DOI":"10.3390\/molecules27248890","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T03:01:51Z","timestamp":1671073311000},"page":"8890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rapid Detection of Recurrent Non-Muscle Invasive Bladder Cancer in Urine Using ATR-FTIR Technology"],"prefix":"10.3390","volume":"27","author":[{"given":"Abdullah I.","family":"El-Falouji","sequence":"first","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia M.","family":"Sabri","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naira M.","family":"Lotfi","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa M.","family":"Medany","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Alaa-eldin","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology for Postgraduate Studies and Research (IBPR), Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr Mounir","family":"Selim","sequence":"additional","affiliation":[{"name":"Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-375X","authenticated-orcid":false,"given":"Asmaa A.","family":"El Leithy","sequence":"additional","affiliation":[{"name":"College of Biotechnology, Misr University for Science and Technology, Giza 12562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5140-1504","authenticated-orcid":false,"given":"Haitham","family":"Kalil","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"},{"name":"Chemistry Department, Cleveland State University, Cleveland, OH 44115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"El-Tobgy","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-5300","authenticated-orcid":false,"given":"Ahmed","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Colonial Foundation Healthy Ageing Centre, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1039\/an9608500779","article-title":"The application of atomic absorption to chemical analysis. A review","volume":"85","author":"David","year":"1960","journal-title":"Analyst"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.14740\/wjon1210","article-title":"Non-muscle invasive bladder cancer: A review of the current trend in Africa","volume":"10","author":"Cassell","year":"2019","journal-title":"World J. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0302-2838(01)00026-4","article-title":"Guidelines on bladder cancer","volume":"41","author":"Oosterlinck","year":"2002","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.eururo.2016.05.041","article-title":"EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016","volume":"71","author":"Babjuk","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0090-4295(00)00555-0","article-title":"Urinary tract infection and patient satisfaction after flexible cystoscopy and urodynamic evaluation","volume":"56","author":"Almallah","year":"2000","journal-title":"Urology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/j.1464-410X.2007.07224.x","article-title":"Patients\u2019 perceived burden of cystoscopic and urinary surveillance of bladder cancer: A randomized comparison","volume":"101","author":"Steyerberg","year":"2008","journal-title":"BJU Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0022-5347(05)65386-4","article-title":"Cost-effectiveness of a modified care protocol substituting bladder tumor markers for cystoscopy for the followup of patients with transitional cell carcinoma of the bladder: A decision analytical approach","volume":"167","author":"Lotan","year":"2002","journal-title":"J. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1093\/ndt\/gfg288","article-title":"The importance of diabetic nephropathy in current nephrological practice","volume":"18","author":"Locatelli","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1002\/pmic.200401334","article-title":"Human urine proteome analysis by three separation approaches","volume":"5","author":"Sun","year":"2005","journal-title":"Proteomics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/mcp.M111.010975","article-title":"A tool for biomarker discovery in the urinary proteome: A manually curated human and animal urine protein biomarker database","volume":"10","author":"Shao","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shaw, R.A., Low-Ying, S., Man, A., Liu, K.-Z., Mansfield, C., Rileg, C.B., and Vijarnsorn, M. (2008). Infrared spectroscopy of biofluids in clinical chemistry and medical diagnostics. Biomedical Vibrational Spectroscopy, John Wiley & Sons, Inc.","DOI":"10.1002\/9780470283172.ch4"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.canlet.2020.02.020","article-title":"Biofluid diagnostics by FTIR spectroscopy: A platform technology for cancer detection","volume":"477","author":"Sala","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1039\/D1AN00546D","article-title":"Detecting antimicrobial resistance in Escherichia coli using benchtop attenuated total reflectance-Fourier transform infrared spectroscopy and machine learning","volume":"146","author":"Wijesinghe","year":"2021","journal-title":"Analyst"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Korb, E., Ba\u011fc\u0131o\u011flu, M., Garner-Spitzer, E., Wiedermann, U., Ehling-Schulz, M., and Schabussova, I. (2020). Machine learning-empowered FTIR spectroscopy serum analysis stratifies healthy, allergic, and SIT-treated mice and humans. Biomolecules, 10.","DOI":"10.3390\/biom10071058"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120857","DOI":"10.1016\/j.talanta.2020.120857","article-title":"Breast cancer detection by ATR-FTIR spectroscopy of blood serum and multivariate data-analysis","volume":"214","author":"Sitnikova","year":"2020","journal-title":"Talanta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120181","DOI":"10.1016\/j.saa.2021.120181","article-title":"Diagnosis of liver cancer by FTIR spectra of serum","volume":"263","author":"Yang","year":"2021","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0266462321000143","article-title":"Early economic evaluation to guide the development of a spectroscopic liquid biopsy for the detection of brain cancer","volume":"37","author":"Gray","year":"2021","journal-title":"Int. J. Technol. Assess. Health Care"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Theakstone, A.G., Brennan, P.M., Jenkinson, M.D., Mills, S.J., Syed, K., Rinaldi, C., Xu, Y., Goodacre, R., Butler, H.J., and Palmer, D.S. (2021). Rapid spectroscopic liquid biopsy for the universal detection of brain tumours. Cancers, 13.","DOI":"10.3390\/cancers13153851"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1039\/C6AN01580H","article-title":"Early diagnosis of Alzheimer\u2019s disease using infrared spectroscopy of isolated blood samples followed by multivariate analyses","volume":"142","author":"Mordechai","year":"2017","journal-title":"Analyst"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yap, X.-L., Wood, B., Ong, T.-A., Lim, J., Goh, B.-H., and Lee, W.-L. (2021). Detection of prostate cancer via IR spectroscopic analysis of urinary extracellular vesicles: A pilot study. Membranes, 11.","DOI":"10.3390\/membranes11080591"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/jbio.201500322","article-title":"Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence","volume":"9","author":"Gok","year":"2016","journal-title":"J. Biophotonics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1021\/acs.analchem.0c04608","article-title":"Ultrarapid on-site detection of SARS-CoV-2 infection using simple ATR-FTIR spectroscopy and an analysis algorithm: High sensitivity and specificity","volume":"93","author":"Barauna","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Paraskevaidi, M., Martin-Hirsch, P.L., and Martin, F.L. (2018). ATR-FTIR spectroscopy tools for medical diagnosis and disease investigation. Nanotechnology Characterization Tools for Biosensing and Medical Diagnosis, Springer.","DOI":"10.1007\/978-3-662-56333-5_4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12117","DOI":"10.1021\/acs.analchem.9b02280","article-title":"Is infrared spectroscopy ready for the clinic?","volume":"91","author":"Finlayson","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1093\/bioinformatics\/btac346","article-title":"Photizo: An open-source library for cross-sample analysis of FTIR spectroscopy data","volume":"38","author":"Cinque","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1021\/ac60214a047","article-title":"Smoothing and differentiation of data by simplified least squares procedures","volume":"36","author":"Savitzky","year":"1964","journal-title":"Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1613\/jair.953","article-title":"SMOTE: Synthetic minority over-sampling technique","volume":"16","author":"Chawla","year":"2002","journal-title":"J. Artif. Intell. Res."},{"key":"ref_28","first-page":"18","article-title":"Classification and regression by randomForest","volume":"2","author":"Liaw","year":"2002","journal-title":"R News"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1016\/j.csda.2007.08.015","article-title":"Empirical characterization of random forest variable importance measures","volume":"52","author":"Archer","year":"2008","journal-title":"Comput. Stat. Data Anal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00345-018-2503-4","article-title":"Molecular markers in bladder cancer","volume":"37","author":"Soria","year":"2019","journal-title":"World J. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.juro.2006.11.066","article-title":"Use of urinary biomarkers for bladder cancer surveillance: Patient perspectives","volume":"177","author":"Yossepowitch","year":"2007","journal-title":"J. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/j.juro.2016.12.010","article-title":"Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study","volume":"197","author":"Kavalieris","year":"2017","journal-title":"J. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"736","DOI":"10.21037\/tau.2018.07.11","article-title":"The value of molecular markers in classification and prediction of progression in non-muscle-invasive bladder cancer","volume":"7","author":"Pan","year":"2018","journal-title":"Transl. Androl. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1158\/1078-0432.CCR-04-2095","article-title":"A molecular signature in superficial bladder carcinoma predicts clinical outcome","volume":"11","author":"Zieger","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrc2222","article-title":"Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis","volume":"7","author":"Menendez","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1039\/C9MO00128J","article-title":"Lipid mechanisms in hallmarks of cancer","volume":"16","author":"Molendijk","year":"2020","journal-title":"Mol. Omics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/cam4.1109","article-title":"Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer","volume":"6","author":"Sahu","year":"2017","journal-title":"Cancer Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1364\/BOE.10.003533","article-title":"Identifying non-muscle-invasive and muscle-invasive bladder cancer based on blood serum surface-enhanced Raman spectroscopy","volume":"10","author":"Chen","year":"2019","journal-title":"Biomed. Opt. Express"},{"key":"ref_39","unstructured":"Beleites, C. (2021). Package \u2018hyperSpec version 0.100.0.\u2019, R Foundation for Statistical Computing."},{"key":"ref_40","unstructured":"Ligges, U., Short, T., Kienzle, P., Schnackenberg, S., Billinghurst, D., Borchers, H.-W., Carezia, A., Dupuis, P., Eaton, J.W., and Farhi, E. (2021). Package \u2018signal version 0.7-7.\u2019, R Foundation for Statistical Computing."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/24\/8890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:15Z","timestamp":1760146875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/24\/8890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":41,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["molecules27248890"],"URL":"https:\/\/doi.org\/10.3390\/molecules27248890","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}