Diagnostic and Prognostic Implications of Ribosomal Protein Transcript Coordination in Human Cancers

Abstract

Ribosomes, the organelles responsible for the translation of mRNA, are comprised of rRNA and ~80 ribosomal proteins (RPs). Although canonically assumed to be maintained in equivalent proportions, some RPs have been shown to possess differential expression across tissue types. Dysregulation of RP expression occurs in a variety of human diseases, notably in many cancers, and altered expression of some RPs correlates with different tumor phenotypes and patient survival. To investigate the impact of global RP transcript (RPT) expression patterns on tumor phenotypes, we analyzed RPT expression of ~10,000 human tumors and 700 normal tissues with t-distributed stochastic neighbor embedding (t-SNE). We show here that normal tissues and cancers possess readily discernible RPT expression patterns. In tumors, this patterning is distinct from normal tissues, distinguishes tumor subtypes from one another, and in many cases correlates with molecular, pathological, and clinical features, including survival. Collectively, RPT expression can be used as a powerful and novel method of tumor classification, offering a potential clinical tool for prognosis and therapeutic stratification.

The roles of moonlight ribosomal proteins in the development of human cancers

“…For many years, scientists believed that unassembled RPs undergo rapid degradation. However, recent findings support the idea that extracellular or intracellular stimuli induce ribosomal stress, which disturbs ribosomal biogenesis followed by the accumulation of free RPs (Dolezal, Dash, & Prochownik, ). RPs participate in multiple extra‐ribosomal functions, including DNA damage repair, apoptosis, cell proliferation and differentiation, drug resistance, and cell migration and invasion (Xu, Xiong, & Sun, ).…”