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A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non-Small Cell Lung Cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Apr 01; Vol. 26 (7), pp. 1725-1735. Date of Electronic Publication: 2019 Nov 15. - Publication Year :
- 2020
-
Abstract
- Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies.<br />Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as "training set"; the remaining two thirds, constituting the "test set," were used for the prospective validation of the GS.<br />Results: In the melanoma training set, the expression level of eight Th1/IFNγ-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications.<br />Conclusions: These findings provide evidence that expression of Th1/IFNγ genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung genetics
Humans
Interferon-gamma metabolism
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms pathology
Melanoma drug therapy
Melanoma genetics
Prognosis
Prospective Studies
Survival Rate
Th1 Cells metabolism
Transcriptome
Biomarkers, Tumor genetics
Carcinoma, Non-Small-Cell Lung pathology
Gene Expression Regulation, Neoplastic
Interferon-gamma immunology
Melanoma pathology
Th1 Cells immunology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31732522
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-18-3717