Caracterização pan-câncer da expressão de genes relacionados ao adesoma em células únicas de tumores humanos

Abstract

Cancer is one of the main challenges when it comes to public health systems around the world, with a significant increase in the number of cases expected in the next three years, including in Brazil. The set of adhesion molecules, the adhesome, is involved in the disease and has been shown to be increasingly relevant to the hallmarks of cancer and also to cachexia; its study still poses challenges given the striking intra- and inter-tumor phenotypic and genotypic diversities. This work aims to characterize the transcriptional profile of the adhesome in single cells from the tumor microenvironment of human tumors. To do this, we reanalyzed single-cell RNA-seq; scRNA-Seq) data, publicly available in the Curated Cancer Cell Atlas database, using the Seurat analysis package (v4.0.6). By analyzing 231 primary tumor samples from previously untreated patients, we evaluated 758,088 unique cells from nine tumor types. Average expression data for 544 adhesome genes were evaluated in seven cell types found in common in pan-cancer data. Cells in the tumor microenvironment showed expression of adhesome genes, and we identified similar patterns of expression among cell types regardless of tumor type. We also identified genes expressed in a cell-specific manner in fibroblasts, endotheliocytes, myeloid and malignant cells. Furthermore, we observed 55 genes significantly correlated with cachexia prevalence, six of which were significantly correlated across multiple cell types. Therefore, we conclude that the tumor microenvironment expresses adhesome genes and that it is possible to identify expression patterns associated with cell types with potential relevance to tumor progression and cachexia. Overall, this work contributes to the understanding of the set of adhesion-related molecules in the tumor microenvironment, which will aid in future studies to determine their mechanisms underlying cachexia and metastasis formation.