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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doaj-80cce6ad2d604a9aa3bc102445bbf2ab2020-11-25T03:39:59ZengMDPI AGCancers2072-66942020-09-01122476247610.3390/cancers12092476Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint TherapiesShaoli Das0Kevin Camphausen1Uma Shankavaram2Bioinformatics core facility, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USABioinformatics core facility, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USABioinformatics core facility, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USATo 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.https://www.mdpi.com/2072-6694/12/9/2476immune signatureimmune checkpoint therapiesimmune prognostic score |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shaoli Das Kevin Camphausen Uma Shankavaram |
spellingShingle |
Shaoli Das Kevin Camphausen Uma Shankavaram Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies Cancers immune signature immune checkpoint therapies immune prognostic score |
author_facet |
Shaoli Das Kevin Camphausen Uma Shankavaram |
author_sort |
Shaoli Das |
title |
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_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_sort |
cancer-specific immune prognostic signature in solid tumors and its relation to immune checkpoint therapies |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-09-01 |
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. |
topic |
immune signature immune checkpoint therapies immune prognostic score |
url |
https://www.mdpi.com/2072-6694/12/9/2476 |
work_keys_str_mv |
AT shaolidas cancerspecificimmuneprognosticsignatureinsolidtumorsanditsrelationtoimmunecheckpointtherapies AT kevincamphausen cancerspecificimmuneprognosticsignatureinsolidtumorsanditsrelationtoimmunecheckpointtherapies AT umashankavaram cancerspecificimmuneprognosticsignatureinsolidtumorsanditsrelationtoimmunecheckpointtherapies |
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