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Dissecting regulated cell death states and transformation mechanisms in the evolutionary trajectory of 30 cancers

Yunpeng Zhang1, Qi Ou1, Congxue Hu1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.

Iscience
|December 4, 2025
PubMed

Insights

This study maps regulated cell death (RCD) in 30 cancer types, revealing pyroptosis and immunogenic cell death are common. Findings offer insights into RCD

Area of Science:

  • Oncology
  • Cell Biology
  • Computational Biology

Background:

  • Cancer is a complex disease characterized by abnormal cell death processes.
  • Understanding regulated cell death (RCD) dysregulation is crucial for cancer progression and treatment.
  • A systematic landscape of RCD states and their evolutionary relationships in tumors is needed.

Purpose of the Study:

  • To characterize the dysregulation of RCD in tumor cells across various cancer types.
  • To depict the evolutionary relationships between different RCD types within cancer cells.
  • To identify key genes and interaction patterns driving RCD evolution in cancer.

Main Methods:

  • Single-cell analysis of 477,766 tumor cells from 458 samples across 30 cancer types.
  • Identification of relationships between 15 RCD states and cancer types.
  • Analysis of interaction patterns, transformation modules, and driver genes related to RCD evolution.

Main Results:

  • Identified 178 relationships between 15 RCD states and cancers.
  • Pyroptosis and immunogenic cell death are prevalent in most cancer types, particularly skin, hematologic, digestive, urological, and lung cancers.
  • Discovered 37 significant interaction patterns, 22 transformation modules, and 153 driver genes linked to RCD evolution in 23 cancer types.

Conclusions:

  • Regulated cell death plays a significant role in cancer progression.
  • The study provides a comprehensive landscape of RCD in cancer, highlighting specific prevalent RCD types.
  • Findings offer insights for developing targeted RCD-based cancer therapies and introduce the "Secret" visual platform.
Keywords:
cancer systems biology

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