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HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer
SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) markedly improve the survival benefits of advanced melanoma and non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients could benefit from such a therapy. Novel and effective clinical biomarkers are needed to assess ICI treatmen...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315784/ https://www.ncbi.nlm.nih.gov/pubmed/35884556 http://dx.doi.org/10.3390/cancers14143495 |
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author | Zhang, Wenjing Lin, Zhijuan Shi, Fuyan Wang, Qiang Kong, Yujia Ren, Yanfeng Lyu, Juncheng Sheng, Chao Li, Yuting Qin, Hao Wang, Suzhen Wang, Qinghua |
author_facet | Zhang, Wenjing Lin, Zhijuan Shi, Fuyan Wang, Qiang Kong, Yujia Ren, Yanfeng Lyu, Juncheng Sheng, Chao Li, Yuting Qin, Hao Wang, Suzhen Wang, Qinghua |
author_sort | Zhang, Wenjing |
collection | PubMed |
description | SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) markedly improve the survival benefits of advanced melanoma and non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients could benefit from such a therapy. Novel and effective clinical biomarkers are needed to assess ICI treatment efficacy. Heparan sulfate proteoglycan 2 (HSPG2) is frequently mutated in melanoma and NSCLC. In this study, we comprehensively integrated the pretreatment somatic mutational profiles and clinical information of both tumors and observed that HSPG2 mutations were associated with favorable tumor immunogenicity and immunotherapeutic efficacy. Our study provides a potential clinical molecular biomarker for evaluating ICI therapy responses. ABSTRACT: Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies. |
format | Online Article Text |
id | pubmed-9315784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93157842022-07-27 HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer Zhang, Wenjing Lin, Zhijuan Shi, Fuyan Wang, Qiang Kong, Yujia Ren, Yanfeng Lyu, Juncheng Sheng, Chao Li, Yuting Qin, Hao Wang, Suzhen Wang, Qinghua Cancers (Basel) Article SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) markedly improve the survival benefits of advanced melanoma and non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients could benefit from such a therapy. Novel and effective clinical biomarkers are needed to assess ICI treatment efficacy. Heparan sulfate proteoglycan 2 (HSPG2) is frequently mutated in melanoma and NSCLC. In this study, we comprehensively integrated the pretreatment somatic mutational profiles and clinical information of both tumors and observed that HSPG2 mutations were associated with favorable tumor immunogenicity and immunotherapeutic efficacy. Our study provides a potential clinical molecular biomarker for evaluating ICI therapy responses. ABSTRACT: Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies. MDPI 2022-07-19 /pmc/articles/PMC9315784/ /pubmed/35884556 http://dx.doi.org/10.3390/cancers14143495 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Wenjing Lin, Zhijuan Shi, Fuyan Wang, Qiang Kong, Yujia Ren, Yanfeng Lyu, Juncheng Sheng, Chao Li, Yuting Qin, Hao Wang, Suzhen Wang, Qinghua HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title | HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title_full | HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title_fullStr | HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title_full_unstemmed | HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title_short | HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer |
title_sort | hspg2 mutation association with immune checkpoint inhibitor outcome in melanoma and non-small cell lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315784/ https://www.ncbi.nlm.nih.gov/pubmed/35884556 http://dx.doi.org/10.3390/cancers14143495 |
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