Abstract 1997: Comparison of gene expression profiling platforms: Translatability of tumor inflammation gene signatures
Authors: Anguiano Esperanza , Desai Keyur , Hayati Sheida , Szabo Peter M. , Pant Saumya , Wang Lisu , Zhang Nancy 
Published: September 2020

Background: A CD8 gene expression signature, developed on a tumor immunology panel (TIP) by BMS as a surrogate marker for inflammation in the tumor microenvironment, was associated with response to immune checkpoint inhibitors in a post-hoc analysis of patients with urothelial carcinoma (CheckMate 275). Similar associations in other tumor types have been assessed using other inflammation signatures (including a tumor inflammation signature [TIS] and a CD8+ T-cell abundance signature [CD8+ TCA]) and gene expression profiling (GEP) platforms (eg, RNA-sequencing [RNA-seq] or GEP panels). This study compares the performance of 4 different GEP panels for assessing tumor inflammation to determine if GEP can be used in a platform-independent manner.

Methods: RNA extracted from unstained commercial formalin-fixed, paraffin-embedded tissue sections (97 melanoma; 101 squamous cell carcinoma of the head and neck) was analyzed using RNA-seq (TruSeq RNA Exome, Illumina) and 2 GEP panels (PanCancer IO 360™ Panel [NanoString] and Oncomine™ Immune Response Research Assay [Thermo Fisher Scientific]). Extraction-free methods were used for the TIP and IOv2 GEP panels. Scores were derived for the CD8, TIS, and CD8+ TCA signatures. CD8+ T cells were quantified using pathologist-supervised, digital scoring–based analysis of CD8 immunohistochemistry (IHC) (Mosaic Laboratories). Programmed death ligand 1 (PD-L1) expression on tumor cells was assessed using the Dako PD-L1 IHC 28-8 pharmDx assay (Agilent).

Results: Correlations were comparable between RNA-seq and GEP panels for 1) expression of each gene in the CD8 signature and 2) CD8 signature scores. The inflammation signatures correlated with CD8 expression by IHC, but not with PD-L1 expression by IHC (Table).

RNA-seq vs panelGEP panelCorrelation of expression of genes in the CD8 signature (median r, IQR)aCorrelation of CD8 signature scores (r)IO 3600.87, 0.78–0.940.95Oncomine IRRA0.82, 0.66–0.860.93TIPb0.71, 0.44–0.830.89IOv2b0.79, 0.40–0.840.86Gene signature vs CD8 IHCGEP panelSignatureNumber of samples (n)Correlation of signature score vs CD8 IHC score (r)IO 360TISc1840.76IO 360CD8+ TCAd1840.69TIPbCD8c1700.80Gene signature vs PD-L1 IHCGEP panelSignatureNumber of samples (n)Correlation of signature score vs PD-L1 IHC score (r)IO 360TISc1870.23TIPbCD8c1720.20aMedian Pearson's r shown for gene-by-gene comparisons in the CD8 signature;bBMS custom panels;cSignature carries investigational use only status when derived using the panel specified;dResearch use only. GEP, gene expression profiling; IHC, immunohistochemistry; IO 360, PanCancer IO 360™ Panel (NanoString); IQR, interquartile range; Oncomine IRRA, Oncomine™ Immune Response Research Assay (Thermo Fisher Scientific); PD-L1, programmed death ligand 1; RNA-seq, RNA-sequencing; TCA, T-cell abundance; TIP, tumor immunology panel; TIS, tumor inflammation signature.

Conclusion: This study shows platform-independent consistency when assessing GEP-derived tumor inflammation signatures and demonstrates the feasibility of utilizing gene expression signatures across GEP platforms.

Citation Format: Esperanza Anguiano, Keyur Desai, Sheida Hayati, Peter M. Szabo, Saumya Pant, Lisu Wang, Nancy Zhang. Comparison of gene expression profiling platforms: Translatability of tumor inflammation gene signatures [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1997.