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 The Cancer Genome Atlas 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.