An absolute human stemness index associated with oncogenic dedifferentiation

Area of Science:

• Cancer biology
• Stem cell research
• Bioinformatics

Background:

• Cancer progression involves acquiring stemness features, crucial for understanding tumor behavior.
• Existing stemness evaluation methods lack intuitive range and are sensitive to technical variations.
• Relative expression orderings (REOs) offer robust gene expression analysis, unaffected by batch effects.

Purpose of the Study:

• To develop and validate an absolute stemness index based on relative expression orderings (REOs).
• To assess the index's performance in evaluating stemness in differentiated cells and cancer tissues.
• To explore the index's correlation with clinical parameters like prognosis and tumor grade.

Main Methods:

• Developed an absolute stemness index utilizing gene pair relative expression orderings (REOs).
• Validated the index against culture time in differentiated stem cells.
• Applied the index to cancer and normal tissue samples to assess differences and intratumor heterogeneity.

Main Results:

• The REO-based stemness index demonstrated higher correlation with stem cell differentiation time compared to previous methods.
• Significant differences in stemness index were observed between cancer and normal tissues, revealing intratumor heterogeneity.
• Higher stemness index values correlated with poorer prognosis and higher histological grade, indicating greater dedifferentiation.

Conclusions:

• The absolute REO-based stemness index provides a robust and intuitive measure of cancer stemness.
• This index effectively differentiates between cancer and normal tissues and captures stemness heterogeneity.
• The stemness index shows potential for assisting tumor grading and has implications for cancer diagnostics and therapeutics.