Identification of a prognostic immune signature for esophageal squamous cell carcinoma to predict survival and inflammatory landscapes

Abstract

BackgroundImmunotherapy has achieved surprising success in the treatment of esophageal squamous cell carcinoma (ESCC). However, studies concerning immune phenotypes within the ESCC microenvironment and their relationship with prognostic outcomes are limited. Therefore, we aim to construct and validate an individual immune-related risk signature for patients with ESCC.MethodsWe collected 196 ESCC cases, including 119 samples from our previous public data (GSE53624) to use as a training set. We additionally collected an independent validation cohort consisting of 77 frozen tumor tissues with qPCR data. Head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) cohorts were also collected for validation. A least absolute shrinkage and selection operator (LASSO) model and a stepwise Cox proportional hazards regression model were used to construct the immune-specific signature. The potential mechanism and inflammatory landscapes of the signature were explored by using bioinformatics and immunofluorescence assay methods.ResultsImmune-related genes were significantly altered in ESCC tissues, and 16 differentially expressed immune-related genes with the most prognostic value were filtered out (P<0.01). Then a six-gene-based signature (TSPAN2, AMBP, ITLN1, C6, PRLR, and MADCAM1) was generated from the training set. This signature classified the patients into two groups with significantly different overall and relapse-free survival. Furthermore, the signature showed similar prognostic values in different clinical subgroups and in the independent cohort, as well as in patients with HNSCC and LUSC. Multivariable Cox regression analysis confirmed that the signature was an independent prognostic factor for patients with ESCC in different cohorts. Pathway analysis showed that genes related to the signature were mostly involved in cell adhesion, leukocyte transendothelial migration, and cancer progression. Further analysis revealed that the signature was closely associated with specific inflammatory activities (activation of macrophages and T cells signaling transduction). Additionally, high-risk patients were found characterized by distinctive immune checkpoints panel and higher filtration of Tregs and fibroblasts. ConclusionWe constructed the first comprehensive immune-related risk signature for ESCC and furnished new hints of immune profiling of ESCC. Future prospective studies are needed to test the clinical utility of this signature in the individualized management of patients with ESCC.

Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes

“…This manuscript has been released as a pre-print at Research Square (He et al, 2020). All authors would like to thank the specimen donors for this study and research groups for the LUSC and HNSCC samples from TCGA.…”

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“…This manuscript has been released as a pre-print at Research Square (He et al, 2020). All authors would like to thank the specimen donors for this study and research groups for the LUSC and HNSCC samples from TCGA.…”