PMID- 35743734 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2075-4426 (Print) IS - 2075-4426 (Electronic) IS - 2075-4426 (Linking) VI - 12 IP - 6 DP - 2022 Jun 10 TI - Machine Learning-Assisted FTIR Analysis of Circulating Extracellular Vesicles for Cancer Liquid Biopsy. LID - 10.3390/jpm12060949 [doi] LID - 949 AB - Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers for cancer liquid biopsy and personalized medicine. Despite this potential, none of the discovered biomarkers has entered the clinical practice so far, and novel approaches for the label-free characterization of EVs are highly demanded. In this regard, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides a quick, reproducible, and informative biomolecular fingerprint of EVs. In this pilot study, we investigated, for the first time in the literature, the capability of FTIR spectroscopy to distinguish between EVs extracted from sera of cancer patients and controls based on their mid-IR spectral response. For this purpose, EV-enriched suspensions were obtained from the serum of patients diagnosed with Hepatocellular Carcinoma (HCC) of nonviral origin and noncancer subjects. Our data point out the presence of statistically significant differences in the integrated intensities of major mid-IR absorption bands, including the carbohydrate and nucleic acids band, the protein amide I and II bands, and the lipid CH stretching band. Additionally, we used Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) for the automated classification of spectral data according to the shape of specific mid-IR spectral signatures. The diagnostic performances of the proposed spectral biomarkers, alone and combined, were evaluated using multivariate logistic regression followed by a Receiving Operator Curve analysis, obtaining large Areas Under the Curve (AUC = 0.91, 95% CI 0.81-1.0). Very interestingly, our analyses suggest that the discussed spectral biomarkers can outperform the classification ability of two widely used circulating HCC markers measured on the same groups of subjects, namely alpha-fetoprotein (AFP), and protein induced by the absence of vitamin K or antagonist-II (PIVKA-II). FAU - Di Santo, Riccardo AU - Di Santo R AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. FAU - Vaccaro, Maria AU - Vaccaro M AUID- ORCID: 0000-0002-4275-0729 AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. FAU - Romano, Sabrina AU - Romano S AD - Dipartimento di Neuroscienze, Sezione di Fisica, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - Di Giacinto, Flavio AU - Di Giacinto F AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. AD - Dipartimento di Neuroscienze, Sezione di Fisica, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - Papi, Massimiliano AU - Papi M AUID- ORCID: 0000-0002-0029-1309 AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. AD - Dipartimento di Neuroscienze, Sezione di Fisica, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - Rapaccini, Gian Ludovico AU - Rapaccini GL AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. AD - Sezione di Medicina Interna, Dipartimento di Medicina e Chirurgia Traslazionale, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - De Spirito, Marco AU - De Spirito M AUID- ORCID: 0000-0003-4260-5107 AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. AD - Dipartimento di Neuroscienze, Sezione di Fisica, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - Miele, Luca AU - Miele L AD - Sezione di Medicina Interna, Dipartimento di Medicina e Chirurgia Traslazionale, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. FAU - Basile, Umberto AU - Basile U AUID- ORCID: 0000-0002-8328-2570 AD - Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. FAU - Ciasca, Gabriele AU - Ciasca G AD - Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy. AD - Dipartimento di Neuroscienze, Sezione di Fisica, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. LA - eng GR - GR-2016-02363310/Ministry of Health, Italy/ PT - Journal Article DEP - 20220610 PL - Switzerland TA - J Pers Med JT - Journal of personalized medicine JID - 101602269 PMC - PMC9224706 OTO - NOTNLM OT - FTIR OT - cancer OT - extracellular vesicles OT - hepatocellular carcinoma OT - liquid biopsy COIS- The authors declare no conflict of interest. EDAT- 2022/06/25 06:00 MHDA- 2022/06/25 06:01 PMCR- 2022/06/10 CRDT- 2022/06/24 01:26 PHST- 2022/05/12 00:00 [received] PHST- 2022/06/01 00:00 [revised] PHST- 2022/06/05 00:00 [accepted] PHST- 2022/06/24 01:26 [entrez] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/06/25 06:01 [medline] PHST- 2022/06/10 00:00 [pmc-release] AID - jpm12060949 [pii] AID - jpm-12-00949 [pii] AID - 10.3390/jpm12060949 [doi] PST - epublish SO - J Pers Med. 2022 Jun 10;12(6):949. doi: 10.3390/jpm12060949.