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Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in

Milcah C Scott1,2,3, Nuri A Temiz1,4, Anne E Sarver5,6

  • 1Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.

Cancer Research
|October 26, 2017
PubMed
Summary

Osteosarcoma (OS) research needs better models. This study found conserved tumor variations across humans, mice, and dogs, linking immune cell absence and proliferation to metastasis and survival in osteosarcoma patients.

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Area of Science:

  • Comparative genomics
  • Cancer biology
  • Translational oncology

Background:

  • Osteosarcoma (OS) patient survival has stagnated, necessitating improved research models.
  • Comparative genomic analysis across species offers a path to understanding OS progression.
  • Large dog breeds and genetically inducible mouse models facilitate OS research.

Purpose of the Study:

  • To investigate conserved intertumor transcriptional variation in osteosarcoma across species.
  • To correlate transcriptional variation with osteosarcoma progression and metastasis.
  • To identify novel biomarkers for improved therapeutic strategies in osteosarcoma.

Main Methods:

  • RNA sequencing of osteosarcoma tumors and cell lines from humans (n=49), mice (n=103), and dogs (n=34).
  • Analysis of conserved intertumor transcriptional variation and associated gene clusters.
  • Development and application of a gene cluster expression summary score (GCESS) to quantify variation.

Main Results:

  • Conserved transcriptional variations related to cell cycle, mitosis, and immune cell presence were identified across species.
  • GCESS values correlated with patient outcomes, with decreased immune cell presence linked to metastasis and poor survival in humans.
  • Findings were validated in an independent human cohort and The Cancer Genome Atlas datasets.

Conclusions:

  • Quantifying tumor heterogeneity, specifically immune cell absence and tumor cell proliferation, can inform osteosarcoma treatment decisions.
  • Novel tools like GCESS can identify prognostic biomarkers for metastatic progression and survival.
  • Cross-species comparative analysis advances understanding and management of osteosarcoma.