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

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.

Analysis of disulfidptosis‐ and cuproptosis‐related LncRNAs in modulating the immune microenvironment and chemosensitivity in colon adenocarcinoma

“…It revealed that the inhibition of glycolysis promotes cuproptosis, highlighting its potential as a promising therapeutic strategy for the treatment of colorectal cancer [13]. Research findings have indicated that the products generated through glycolysis have the capacity to modulate the activity of disulfidptosis and cuproptosis pathways, ultimately influencing the fate of tumour cells [14, 15]. Given the intricate correlation between programmed cell death (disulfidptosis and cuproptosis) and glucose metabolism, we decided to explore the potential interaction between disulfidptosis‐ and cuproptosis‐related lncRNAs in the pathogenesis of COAD.…”

A disulfidptosis-related glucose metabolism and immune response prognostic model revealing the immune microenvironment in lung adenocarcinoma

“…This process can reduce the toxicity of cystine and provide raw materials for the synthesis of glutathione. However, when glucose is deficient, NADPH depletion leads to abnormal accumulation of cystine and other disulfides in cells highly expressing SLC7A11 and triggers disulfidptosis ( 17 ). As a species of high-metabolism and high-energy-consumption cell, tumor cells with high SLC7A11 expression exhibit a stronger disulfidptosis response when glucose is depleted ( 18 ).…”

A novel model combining genes associated with disulfidptosis and glycolysis to predict breast cancer prognosis, molecular subtypes, and treatment response

“…5 Given the strong relationship between the two pathways and their ability to combat cancer, they have been identified as valuable indicators for predicting colorectal cancer prognosis and immunotherapy response. 13 Their ability and mechanism in BC, however, are unknown.…”