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Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies

To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pa...

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Autores principales: Das, Shaoli, Camphausen, Kevin, Shankavaram, Uma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563367/
https://www.ncbi.nlm.nih.gov/pubmed/32882873
http://dx.doi.org/10.3390/cancers12092476
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author Das, Shaoli
Camphausen, Kevin
Shankavaram, Uma
author_facet Das, Shaoli
Camphausen, Kevin
Shankavaram, Uma
author_sort Das, Shaoli
collection PubMed
description To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pan-cancer transcriptomic signature showed two major immune function types: one related to NK-, T-, and B-cell functions and the other related to monocyte, macrophage, dendritic cell, and Toll-like receptor functions. Kaplan–Meier analysis showed differential prognosis of these two groups, dependent on the cancer type. Our analysis of TCGA solid tumors with an elastic net model identified 155 genes associated with disease-free survival in different tumor types with varied influence across different cancer types. With this gene set, we computed cancer-specific prognostic immune score models for individual cancer types that predicted disease-free and overall survival. Validation of our model on available published data of immune checkpoint blockade therapies on melanoma, kidney renal cell carcinoma, non-small cell lung cancer, gastric cancer and bladder cancer confirmed that cancer-specific higher immune scores are associated with response to immunotherapy. Our analysis provides a comprehensive map of cancer-specific immune-related prognostic gene sets that are associated with immunotherapy response.
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spelling pubmed-75633672020-10-27 Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies Das, Shaoli Camphausen, Kevin Shankavaram, Uma Cancers (Basel) Article To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pan-cancer transcriptomic signature showed two major immune function types: one related to NK-, T-, and B-cell functions and the other related to monocyte, macrophage, dendritic cell, and Toll-like receptor functions. Kaplan–Meier analysis showed differential prognosis of these two groups, dependent on the cancer type. Our analysis of TCGA solid tumors with an elastic net model identified 155 genes associated with disease-free survival in different tumor types with varied influence across different cancer types. With this gene set, we computed cancer-specific prognostic immune score models for individual cancer types that predicted disease-free and overall survival. Validation of our model on available published data of immune checkpoint blockade therapies on melanoma, kidney renal cell carcinoma, non-small cell lung cancer, gastric cancer and bladder cancer confirmed that cancer-specific higher immune scores are associated with response to immunotherapy. Our analysis provides a comprehensive map of cancer-specific immune-related prognostic gene sets that are associated with immunotherapy response. MDPI 2020-09-01 /pmc/articles/PMC7563367/ /pubmed/32882873 http://dx.doi.org/10.3390/cancers12092476 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Das, Shaoli
Camphausen, Kevin
Shankavaram, Uma
Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title_full Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title_fullStr Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title_full_unstemmed Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title_short Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
title_sort cancer-specific immune prognostic signature in solid tumors and its relation to immune checkpoint therapies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563367/
https://www.ncbi.nlm.nih.gov/pubmed/32882873
http://dx.doi.org/10.3390/cancers12092476
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