Gradient boosting reveals spatially diverse cholesterol gene signatures in colon cancer DOI Creative Commons

Xiuxiu Yang,

Debolina Chatterjee,

Justin L. Couetil

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 29, 2024

Colon cancer (CC) is the second most common cause of deaths and fourth prevalent in United States. Recently cholesterol metabolism has been identified as a potential therapeutic avenue due to its consistent association with tumor treatment effects overall prognosis. We conducted differential gene analysis KEGG pathway on paired adjacent-normal samples from TCGA Adenocarcinoma project, identifying that bile secretion was only significantly downregulated pathway. To evaluate relationship between CC prognosis, we used genes this several statistical models like Cox proportional Hazard (CPH), Random Forest (RF), Lasso Regression (LR), eXtreme Gradient Boosting (XGBoost) identify which contributed highly predictive ability all models, ADCY5, SLC2A1. demonstrate using XGBoost improves stratification patients into low high-risk groups compared traditional CPH, RF LR models. Spatial transcriptomics (ST) revealed SLC2A1 (glucose transporter 1, GLUT1) colocalized small blood vessels. ADCY5 localized stromal regions both ST protein immunohistochemistry. Interestingly, these significant are expressed tissues other than itself, highlighting complex interplay microenvironment, druggable targets may be found modify how "normal" tissue interacts tumors.

Language: Английский

Gradient boosting reveals spatially diverse cholesterol gene signatures in colon cancer DOI Creative Commons

Xiuxiu Yang,

Debolina Chatterjee,

Justin L. Couetil

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 29, 2024

Colon cancer (CC) is the second most common cause of deaths and fourth prevalent in United States. Recently cholesterol metabolism has been identified as a potential therapeutic avenue due to its consistent association with tumor treatment effects overall prognosis. We conducted differential gene analysis KEGG pathway on paired adjacent-normal samples from TCGA Adenocarcinoma project, identifying that bile secretion was only significantly downregulated pathway. To evaluate relationship between CC prognosis, we used genes this several statistical models like Cox proportional Hazard (CPH), Random Forest (RF), Lasso Regression (LR), eXtreme Gradient Boosting (XGBoost) identify which contributed highly predictive ability all models, ADCY5, SLC2A1. demonstrate using XGBoost improves stratification patients into low high-risk groups compared traditional CPH, RF LR models. Spatial transcriptomics (ST) revealed SLC2A1 (glucose transporter 1, GLUT1) colocalized small blood vessels. ADCY5 localized stromal regions both ST protein immunohistochemistry. Interestingly, these significant are expressed tissues other than itself, highlighting complex interplay microenvironment, druggable targets may be found modify how "normal" tissue interacts tumors.

Language: Английский

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