Genome-scale CRISPR-Cas9 screening stratifies pancreatic cancer with distinct outcomes and immunotherapeutic efficacy

Wang, Libo; Fu, De Liang; Weng, Siyuan; Xu, Hui; Liu, Long; Guo, Chunguang; Ren, Yuqing; Han, Xinwei

doi:10.1016/j.cellsig.2023.110811

Cited by 2 publications

(1 citation statement)

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“…It has been widely used in fields such as genetic diseases, infectious diseases, and tumors, providing a promising solution for the treatment of various diseases [ 25 ]. Wang et al identified cancer essential genes (CEGs) with prognostic value through CRISPR-Cas9 screening, established and validated three distinct subtypes of pancreatic cancer (PC) patients in a multicenter study [ 26 ]. These findings not only deepen our understanding of PC molecular heterogeneity but also address the clinical need for risk stratification and personalized treatment in the era of precision medicine.…”

Section: Discussionmentioning

confidence: 99%

Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer

Yang,

Liu,

Wang

et al. 2024

J Transl Med

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Background The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. Methods we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. Findings We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. Interpretation The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

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Section: Discussionmentioning

confidence: 99%