Application of Mass Cytometry in Multiparametric Characterization of Precancerous Cervical Lesions

Pešut, Ena; Šimić, Ivana; Kužilkova, Daniela; Kalina, Tomas; Fureš, Rajko; Erceg Ivkošić, Ivana; Milutin Gašperov, Nina; Sabol, Ivan (2024) Application of Mass Cytometry in Multiparametric Characterization of Precancerous Cervical Lesions. Cytometry Part B: Clinical Cytometry . ISSN 1552-4949 (In Press)

PDF - Accepted Version - article Restricted to Registered users only until 27 October 2025. Download (4MB) | Request a personal copy from author

Abstract

Introduction: Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Methods: Liquid-based cytology (LBC) cervical samples were collected (N=53) from women categorized as normal and precancerous lesions. Human papillomavirus (HPV) was genotyped by PCR, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman’s rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Results: Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18 and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p=0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p=0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low and high grade intraepithelial lesion cases (LSIL and HSIL). Conclusions: CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.

Item Type:	Article
Uncontrolled Keywords:	cervical cancer; markers; HPV; mass cytometry
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Cytology, Histology and Embryology BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences > Clinical Cytology BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences > Pathophysiology
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Multifaktorna analiza HPV inficiranih stanica u nastanku raka vrata maternice-MACCD Ivan Sabol; Ivana Erceg Ivkošić; Rajko Fureš; Tomaš Kalina; Branka Molnar Stantić IP-2019-04-3403 HRZZ
Depositing User:	Ivan Sabol
Date Deposited:	07 Nov 2024 12:44
URI:	http://fulir.irb.hr/id/eprint/9179
DOI:	10.1002/cyto.b.22211

Actions (login required)

View Item