Proteomic alterations in early stage cervical cancer
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Coşkun Güzel1, Natalia I. Govorukhina2, G. Bea A. Wisman3, Christoph Stingl1, Lennard J.M. Dekker1, Harry G. Klip3, Harry Hollema4, Victor Guryev2, Peter L. Horvatovich2, Ate G.J. van der Zee3, Rainer Bischoff2 and Theo M. Luider1
1Laboratory of Neuro-Oncology, Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam 3015 CN, The Netherlands
2Department of Analytical Biochemistry, Center for Pharmacy, University of Groningen, Groningen 9713 AV, The Netherlands
3Department of Gynecologic Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands
4Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands
Theo M. Luider, email: firstname.lastname@example.org
Keywords: LCM; cervical cancer; biomarker; PRM; proteomics
Received: November 01, 2017 Accepted: February 25, 2018 Published: April 06, 2018
Laser capture microdissection (LCM) allows the capture of cell types or well-defined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue (n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by “all-or-nothing” analysis, Bonferroni, and Benjamini-Hochberg correction for multiple testing. By comparing LCM cell type preparations, 31 proteins were exclusively found in early stage cervical cancer (n = 11) when compared with healthy epithelium and stroma, based on criteria that address specificity in a restrictive “all-or-nothing” way. By Bonferroni correction for multiple testing, 30 proteins were significantly up-regulated between early stage cervical cancer and healthy control, including six members of the MCM protein family. MCM proteins are involved in DNA repair and expected to be participating in the early stage of cancer. After a less stringent Benjamini-Hochberg correction for multiple testing, we found that the abundances of 319 proteins were significantly different between early stage cervical cancer and healthy controls. Four proteins were confirmed in digests of whole tissue lysates by Parallel Reaction Monitoring (PRM). Ingenuity Pathway Analysis using correction for multiple testing by permutation resulted in two networks that were differentially regulated in early stage cervical cancer compared with healthy tissue. From these networks, we learned that specific tumor mechanisms become effective during the early stage of cervical cancer.
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