A novel disulfidptosis and glycolysis related risk score signature for prediction of prognosis and ICI therapeutic responsiveness in colorectal cancer

Abstract

Abstract Disulfidptosis is a newly-identified non-programmed cell death mode with tight associations with glucose metabolism. Elevated glycolysis is an important metabolic feature of tumor cells, which fulfills the energy requirement for their rapid growth and progression. Our present study determined to develop a disulfidptosis and glycolysis related gene (DGRG) risk score signature to predict the prognosis and ICI therapeutic responsiveness for CRC patients. First, the gene expression and clinical profiles for CRC patients were obtained from TCGA and GEO database. Using weighted gene co-expression network analysis, we identified hub genes showing the strongest correlations with both disulfidptosis and glycolysis activities. Next, a DGRG risk score signature was successfully developed through univariate and least absolute shrinkage and selection operator method Cox regression method. A DGRG risk score-based nomogram could further enhance the predictive performance. In addition, an array of systemic analysis was performed to unravel the correlation of DGRG risk score with tumor microenvironment. The results showed that CRC patients with low DGRG risk level had up-regulated immune cell infiltrations, enhanced metabolic activities and heightened gene mutation frequencies, while high risk patients was the opposite. Moreover, our present study identified low risk CRC patients as potential beneficiaries from immune checkpoint inhibitor (ICI) therapies. Our present work highlighted the potential utility of DGRG risk score signature in prognosis prediction and ICI responsiveness determination for CRC patients, which demonstrated promising clinical application value.