# Ribosome Biogenesis Underpins Tumor Progression: A Comprehensive Signature for Survival and Immunotherapy Response Prediction

## TL;DR

This study shows that high ribosome activity in tumors is linked to worse survival and cancer progression, but may also predict better response to immunotherapy.

## Contribution

The OncoRibo-68 score is introduced as a novel biomarker for predicting cancer prognosis and immunotherapy response.

## Key findings

- Higher OncoRibo-68 scores correlate with worse overall and progression-free survival in multiple cancers.
- Elevated OncoRibo-68 scores are associated with an immunosuppressive tumor environment and increased checkpoint inhibitor response.
- The OncoRibo-68 score is a promising tool for risk stratification and treatment selection in cancer patients.

## Abstract

Ribosome Biogenesis (RiBi) is the process by which cells create the molecular machinery needed to assemble amino acids into proteins. Because cancer cells divide quickly, they often have higher RiBi activity; this can drive their aggressiveness and reduce patients’ survival. To understand this better, we developed RiBi scores (PanRibo-515 and OncoRibo-68) that capture overall RiBi activity in tumors. We tested both scores in several cancer patient datasets, including those with immunotherapy treatments, and found that higher scores were linked to worse outcomes. By measuring key genes in RiBi, we can more accurately predict which tumors are likely to progress faster or respond to immunotherapy. This research could help with identification of patients who need alternate treatment approaches or could be matched to targeted therapies, ultimately improving patient care.

Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes. Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis. Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors. Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy.