The expression signature of cancer-associated KRAB-ZNF factors identified in TCGA pan-cancer transcriptomic data

Przemysław Biecek , Rafał Cylwa , Marta Gładych , Kornel Kiełczewski , Triantafillos Liloglou , Andrzej Mackiewicz , Urszula Oleksiewicz

Abstract

The KRAB-ZNF (Krüppel-associated box domain zinc finger) gene family is composed of a large number of highly homologous genes, gene isoforms, and pseudogenes. The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Due to its high complexity, the KRAB-ZNF family has not been studied in sufficient detail, and the involvement of its members in carcinogenesis remains mostly unexplored. In this study, we aimed to provide a comprehensive description of cancer-associated KRAB-ZNFs using publicly available TCGA pan-cancer datasets. We analyzed 6727 tumor and normal tissue samples from 16 cancer types. Here, we showed that a small but distinctive cluster of 16 KRAB-ZNFs is commonly upregulated across multiple cancer cohorts in comparison to normal samples. We confirmed these observations in the independent panels of lung and breast cancer cell lines and tissues. This upregulation was also observed for most of the KRAB-ZNF splicing variants, whose expression is simultaneously upregulated in tumors compared to normal tissues. Finally, by analyzing the clinicopathological data for breast and lung cancers, we demonstrated that the expression of cancer-associated KRAB-ZNFs correlates with patient survival, tumor histology, and molecular subtyping. Altogether, our study allowed the identification and characterization of KRAB-ZNF factors that may have an essential function in cancer biology and thus, potential to become novel oncologic biomarkers and treatment targets.
Author Przemysław Biecek (FMIS / DCSDCAM)
Przemysław Biecek,,
- Department of CAD/CAM Systems Design and Computer-Aided Medicine
, Rafał Cylwa
Rafał Cylwa,,
-
, Marta Gładych
Marta Gładych,,
-
, Kornel Kiełczewski (FMIS)
Kornel Kiełczewski,,
- Faculty of Mathematics and Information Science
, Triantafillos Liloglou
Triantafillos Liloglou,,
-
, Andrzej Mackiewicz
Andrzej Mackiewicz,,
-
, Urszula Oleksiewicz (FMIS)
Urszula Oleksiewicz,,
- Faculty of Mathematics and Information Science
Journal seriesMolecular Oncology, ISSN 1574-7891, (A 40 pkt)
Issue year2018
Vol1
Pages1-40
Publication size in sheets1.95
Keywords in Polishrak płuca, rak piersi, czynniki KRAB, TCGA
Keywords in EnglishTCGA , KRAB-ZNF, breast cancer, cancer, epigenetics, lung cancer
ASJC Classification1306 Cancer Research; 1311 Genetics; 1313 Molecular Medicine; 2700 General Medicine
Abstract in PolishPraca dotyczy analizy czynników KRAB i ich związku z przeżywalnością dla różnych nowotworów. Przeprowadzono analizę z użyciem publicznie dostępnych danych TCGA. Główne wyniki pracy pozwalają na lepsze zrozumienie które czynniki z rodziny KRAB korelują z przeżyciem. Z uwagi na wielkość analizowanych kohort bardziej szczegółowe wyniki uzyskano dla raka płuc i raka piersi. Warto może dodać, że te wyniki pochodzą z badań które prowadzimy od 2016 roku wspólnie ze studentami i magistrantami z SMADu.
DOIDOI:10.1002/1878-0261.12407
URL https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/1878-0261.12407
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 40.0, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.119; WoS Impact Factor: 2016 = 5.314 (2) - 2016=5.957 (5); WoS Citations = 0
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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