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DEPTH2: an mRNA-based algorithm to evaluate intratumor heterogeneity without reference to normal controls.

Dandan Song1,2,3, Xiaosheng Wang4,5,6

  • 1Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.

Journal of Translational Medicine
|April 2, 2022
PubMed
Summary
This summary is machine-generated.

A new algorithm, DEPTH2, effectively measures intratumor heterogeneity (ITH) using mRNA data. DEPTH2 ITH correlates with poor prognosis and treatment resistance, offering a promising tool for cancer evaluation.

Keywords:
AlgorithmAntitumor immunityCancer prognosisGene expression profilesGenomic instabilityIntratumor heterogeneity

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Area of Science:

  • Oncology
  • Genomics
  • Bioinformatics

Background:

  • Intratumor heterogeneity (ITH) is a critical factor in cancer progression, influencing prognosis, immune evasion, and treatment resistance.
  • Accurate evaluation of ITH is essential for effective cancer diagnosis and personalized treatment strategies.

Purpose of the Study:

  • To introduce DEPTH2, a novel mRNA-based algorithm for evaluating intratumor heterogeneity (ITH) without requiring normal tissue samples.
  • To assess the performance of DEPTH2 in measuring ITH across various cancer types and its association with clinical outcomes.

Main Methods:

  • Developed DEPTH2, an algorithm that quantifies ITH based on the standard deviations of absolute z-scored transcriptome levels within tumors.
  • Applied DEPTH2 to analyze 33 cancer types from The Cancer Genome Atlas (TCGA) cohort.

Main Results:

  • DEPTH2 effectively measured ITH, demonstrating significant associations with tumor progression, unfavorable prognosis, and genomic instability across diverse cancers.
  • DEPTH2 ITH showed strong correlations with reduced antitumor immunity, poorer immunotherapy response, and altered drug responses.
  • Compared to existing algorithms (MATH, PhyloWGS, ABSOLUTE, DEPTH, tITH), DEPTH2 exhibited superior or competitive performance in predicting clinical outcomes and characterizing ITH properties.

Conclusions:

  • DEPTH2 provides a robust and effective method for assessing intratumor heterogeneity (ITH) using readily available mRNA data.
  • The DEPTH2 algorithm shows broad applicability and is expected to be a valuable tool for cancer research and clinical practice, potentially surpassing other existing ITH evaluation methods.