Τίτλος:
A Th1/IFNG gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. 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. Results: In the melanoma training set, the expression level of eight Th1/IFNg-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/IFNg -related genes was associated with the presence of lymphocytes in tumor samples in both indications. Conclusions: These findings provide evidence that expression of Th1/IFNg 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. © 2019 American Association for Cancer Research.
Συγγραφείς:
Dizier, B.
Callegaro, A.
Debois, M.
Dreno, B.
Hersey, P.
Gogas, H.J.
Kirkwood, J.M.
Vansteenkiste, J.F.
Sequist, L.V.
Atanackovic, D.
Goeman, J.
van Houwelingen, H.
Salceda, S.
Wang, F.
Therasse, P.
Debruyne, C.
Spiessens, B.
Brichard, V.G.
Louahed, J.
Ulloa-Montoya, F.
Περιοδικό:
Clinical Cancer Research
Εκδότης:
American Association for Cancer Research Inc.
Λέξεις-κλειδιά:
gamma interferon; tumor marker, adult; Article; cancer prognosis; cancer surgery; controlled study; disease free survival; high risk patient; human; lymph node metastasis; major clinical study; melanoma; non small cell lung cancer; overall survival; priority journal; prospective study; protein expression level; Th1 cell; tumor associated leukocyte
DOI:
10.1158/1078-0432.CCR-18-3717
