The Convergent Cancer Evolution toward a Single Cellular Destination.

Area of Science:

• Evolutionary biology
• Cancer research
• Developmental biology

Background:

• Darwin's theory posits evolution driven by random mutations and natural selection, typically without a predefined direction.
• Cancer research often integrates developmental and evolutionary concepts, yet these philosophies can appear incompatible.
• Understanding the evolutionary trajectory of cancers is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the evolutionary path of solid tumor cancers.
• To determine if cancer evolution follows a directional trend toward a specific cellular state.
• To explore the relationship between this evolutionary trend and cancer prognosis.

Main Methods:

• Constructed a functional space of human cells using gene expression data from 107 cell types.
• Traced the evolutionary trajectory of 18 types of solid tumor cancers within this functional space.
• Analyzed evolutionary trends by excluding known cancer/ESC signature genes and oncogenic gene sets.

Main Results:

• A dominant trend toward the functional status of embryonic stem cells (ESC) was observed in approximately 3,000 tumors across diverse tissue environments.
• This ESC-centric evolutionary pattern persisted even after excluding significant gene sets, indicating robust convergence.
• The functional distance to ESC emerged as a common prognostic indicator, with shorter distances correlating with poorer patient outcomes.

Conclusions:

• Cancer evolution appears to be a directional process, converging toward a defined cellular destination (ESC status), irrespective of the external tumor environment.
• This finding reconciles developmental and evolutionary perspectives in cancer research.
• The study opens new avenues for inquiry in evolutionary biology and cancer prognostication.