期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 13, 页码 7338-7346出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1916960117
关键词
REIMS; cervical cancer; mass spectrometry; iKnife; fertility preservation
资金
- Medical Research Council's Imperial Confidence in Concept Scheme [PS2857, PS2897]
- European Research Council Consolidator GrantMASSLIP [CoG 617896]
- Biomedical Research Centre Cancer Imperial College [P83204]
- Imperial College Healthcare Charity [RF16\10001]
- British Society for Colposcopy and Cervical Pathology
- National Research Development and Innovation Office of Hungary [KNN121510, NVKP_16-1-2016-0042]
- Waters Corporation [P53626_WSSB]
Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) +/- cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV +/- CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV +/- CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
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