SERS-based differential diagnosis between multiple solid malignancies: breast, colorectal, lung, ovarian and oral cancer

Vlad Moisoiu,1,2,* Andrei Stefancu,1,3,*Diana Gulei,3,* Radu Boitor,4 Lorand Magdo,2,5 Lajos Raduly,5,6 Sergiu Pasca,2 Paul Kubelac,2,7 Nikolay Mehterov,8,9 Vasile Chiș,1 Marioara Simon,10 Mihai Muresan,2,11–12 Alexandra Iulia Irimie,13 Mihaela Baciut,14 Rares Stiufiuc,3,15 Ioana E Pavel,3,16 Patriciu Achimas-Cadariu,17,18 Calin Ionescu,2,11 Vladimir Lazar,19 Victoria Sarafian,8,9 Ioan Notingher,4 Nicolae Leopold,1,3 Ioana Berindan-Neagoe3,5,201Faculty of Physics, Babeș-Bolyai University, Cluj-Napoca, Romania; 2Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3MedFuture - Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4School of Physics and Astronomy, University of Nottingham, Nottingham, UK; 5Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 6Department of Pathophysiology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 7Department of Medical Oncology, Prof. Dr. Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania; 8Department of Medical Biology, Faculty of Medicine, Medical University-Plovdiv, Plovdiv, Bulgaria; 9Technological Center for Emergency Medicine, Plovdiv, Bulgaria; 10Department of Bronchology, Leon Daniello Pneumophysiology Clinical Hospital, Cluj-Napoca, Romania; 115th Surgical Department, Cluj-Napoca Municipal Hospital, Cluj-Napoca, Romania; 12Department of Surgical and Gynecological Oncology, Prof. Dr. Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania; 13Department of Prosthetic Dentistry and Dental Materials, Division Dental Propaedeutics, Aesthetics, Faculty of Dentistry, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 14Department of Cranio-Maxillofacial Surgery and Dental Emergencies, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 15Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 16Department of Chemistry, Wright State University, Dayton, OH, USA; 17Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 18Department of Surgical Oncology, Prof. Dr. Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania; 19Worldwide Innovative Network for Personalized Cancer Therapy, Villejuif, France; 20Department of Functional Genomics and Experimental Pathology, Prof. Dr. Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania*These authors contributed equally to this workPurpose: Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer.Patients and methods: Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis–linear discriminant analysis (PCA-LDA).Results: The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer.Conclusion: SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.Keywords: surface-enhanced Raman scattering, SERS, serum, principal component analysis-linear discriminant analysis, solid malignancies