Radiomics Biomarkers Correlate with CD8 Expression and Predict Immune Signatures in Melanoma Patients

Mol Cancer Res. 2021 Jun;19(6):950-956. doi: 10.1158/1541-7786.MCR-20-1038. Epub 2021 Apr 2.

Abstract

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers. PET/CT scans from 52 patients with stage III/IV melanoma were assessed and CT image parameters were evaluated as prognostic biomarkers. Analysis indicated patients with high standard deviation or high mean of positive pixels (MPP) had worse progression-free survival (P = 0.00047 and P = 0.0014, respectively) and worse overall survival (P = 0.0223 and P = 0.0465, respectively). Whole-exome sequencing showed high MPP was associated with BRAF mutation status (P = 0.0389). RNA-sequencing indicated patients with immune "cold" signatures had worse survival, which was associated with CT biomarker, MPP4 (P = 0.0284). Multiplex immunofluorescence confirmed a correlation between CD8 expression and image biomarkers (P = 0.0028). IMPLICATIONS: CT parameters have the potential to be cost-effective biomarkers of survival in melanoma, and reflect the tumor immune-microenvironment. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/950/F1.large.jpg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Exome Sequencing / methods
  • Humans
  • Immunotherapy / methods
  • Kaplan-Meier Estimate
  • Melanoma / diagnostic imaging*
  • Melanoma / genetics
  • Melanoma / therapy
  • Mutation
  • Positron Emission Tomography Computed Tomography / methods*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • RNA-Seq / methods
  • Skin Neoplasms / diagnostic imaging*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / therapy
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)