“In the light of evolution:” keratins as exceptional tumor biomarkers

Abstract

Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into “soft” and “hard” keratins. They have a key role in several aspects of cancer pathophysiology, including cancer cell invasion and metastasis, and several members of the KRT family serve as diagnostic or prognostic markers. The human genome contains both, functional KRT genes and non-functional KRT pseudogenes, arranged in two uninterrupted clusters on chromosomes 12 and 17. This characteristic renders KRTs ideal for evolutionary studies. Herein, comprehensive phylogenetic analyses of KRT homologous proteins in the genomes of major taxonomic divisions were performed, so as to fill a gap in knowledge regarding the functional implications of keratins in cancer biology among tumor-bearing species. The differential expression profiles of KRTs in diverse types of cancers were investigated by analyzing high-throughput data, as well. Several KRT genes, including the phylogenetically conserved ones, were found to be deregulated across several cancer types and to participate in a common protein-protein interaction network. This indicates that, at least in cancer-bearing species, these genes might have been under similar evolutionary pressure, perhaps to support the same important function(s). In addition, semantic relations between KRTs and cancer were detected through extensive text mining. Therefore, by applying an integrative in silico pipeline, the evolutionary history of KRTs was reconstructed in the context of cancer, and the potential of using non-mammalian species as model organisms in functional studies on human cancer-associated KRT genes was uncovered.

METI: Deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics

“…2f , METI effectively identifies all tumor regions in STAD sample G2, in strong agreement with annotations made by our experienced pathologists. Next, METI incorporates additional markers to characterize cancer cell states and heterogeneity, including markers of cell proliferation such as MKI67 to map proliferative cancer cells, stemness-related markers such as SOX9 to identify stem-like cancer cells in STAD, and therapeutic targets like CLDN18 and MSLN to further characterize tumor subtypes [32-35]. These aforementioned marker genes exhibit distinct expression patterns within the tumor region of sample G2, as illustrated in Fig.…”

Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome

“…However, we were able to identify 13 species with >0.1% average abundance across all samples. Although the species-correlated genes did not all fall into any pathway classification or protein class, the correlation of eight of these species with the keratin gene KRT77 is intriguing, since KRT77 is considered a biomarker for squamous cell carcinoma [72] and involved in the epithelial differentiation from the limbal stem cells [73].…”

Patterns of low-complexity regions in human genes

“…Keratin proteins participate in a variety of functions in the cytoskeletal system, epithelial tissues, and morphological features and provide mechanical stability to tissues (48,51). Recent investigations have underscored the pivotal role of keratins in numerous hereditary diseases as well as in the context of various cancers (52)(53)(54). The presence of glycine-rich regions within keratins suggests a potential involvement of LCR in enhancing the interacting capabilities of these proteins in various functional contexts.…”