Cytokeratin 19 role in malignancy: a systematic review

Cytokeratin 19 (CK19) has emerged as an important biomarker in epithelial malignancies. Its expression is closely linked to cellular differentiation, tumor aggressiveness, and metastatic potential. This systematic review aimed to comprehensively evaluate CK19 expression across human malignant cell lines and assess its potential diagnostic, prognostic, and therapeutic implications. A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to September 2024. Using a combination of MeSH terms and keywords “Cytokeratin 19”, “Cell line”, “Cell culture”), studies reporting CK19 expression in human malignant cell lines were identified. Only English-language publications were included. Data from the included articles were extracted and tabulated. A total of 3205 articles were initially identified, with 264 studies ultimately meeting the inclusion criteria after duplicate and irrelevant publication removal. These studies evaluated CK19 expression across 476 human malignant cell lines from 32 different cancer types. In epithelial-derived tumors, notably breast, liver, and colorectal cancers, cell lines such as MCF-7, T47D, and SKBR3 consistently demonstrated high CK19 positivity, whereas MDA-MB-231 and other lines exhibited variable expression. In contrast, several lung cancer cell lines and specific non-epithelial models displayed low or absent CK19 levels. The analysis also revealed that CK19 expression is modulated by various treatments: chemotherapeutic agents, epigenetic modifiers, and targeted compounds were shown to either upregulate or downregulate its expression. CK19 is a critical biomarker in a wide array of epithelial malignancies. Its differential expression correlates with tumor differentiation, metastatic behavior, and therapeutic response. These findings underscore the importance of further clinical research to validate CK19 as a diagnostic and prognostic tool, as well as a potential therapeutic target in personalized cancer management.