Cargando…

The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma

SIMPLE SUMMARY: In this study, we focused on exploring phagocytosis regulators’ expression and mutational characteristics in skin cutaneous melanoma samples and delineating two molecular subtypes based on expression characteristics. We determined the relationship between phagocytosis regulators and...

Descripción completa

Detalles Bibliográficos
Autores principales: Xing, Jiahua, Guo, Lingli, Jia, Ziqi, Li, Yan, Han, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331497/
https://www.ncbi.nlm.nih.gov/pubmed/35892841
http://dx.doi.org/10.3390/cancers14153582
_version_ 1784758418925420544
author Xing, Jiahua
Guo, Lingli
Jia, Ziqi
Li, Yan
Han, Yan
author_facet Xing, Jiahua
Guo, Lingli
Jia, Ziqi
Li, Yan
Han, Yan
author_sort Xing, Jiahua
collection PubMed
description SIMPLE SUMMARY: In this study, we focused on exploring phagocytosis regulators’ expression and mutational characteristics in skin cutaneous melanoma samples and delineating two molecular subtypes based on expression characteristics. We determined the relationship between phagocytosis regulators and survival by survival analysis of molecular subtypes. We then constructed a survival model (PRRS) to further quantify the criteria. Moreover, we combined pathway analysis, immune infiltration analysis, and mutation analysis to deeply explore the effects of phagocytosis regulators on skin cutaneous melanoma samples. ABSTRACT: Tumor-associated macrophages (TAMs) have gained considerable attention as therapeutic targets. Monoclonal antibody treatments directed against tumor antigens contribute significantly to cancer cell clearance by activating macrophages to phagocytose tumor cells. Due to its complicated genetic and molecular pathways, skin cutaneous melanoma (SKCM) has not yet attained the expected clinical efficacy and prognosis when compared to other skin cancers. Therefore, we chose TAMs as an entrance point. This study aimed to thoroughly assess the dysregulation and regulatory role of phagocytosis regulators in SKCM, as well as to understand their regulatory patterns in SKCM. This study subtyped prognosis-related phagocytosis regulators to investigate prognostic differences between subtypes. Then, we screened prognostic factors and constructed phagocytosis-related scoring models for survival prediction using differentially expressed genes (DEGs) between subtypes. Additionally, we investigated alternative treatment options using chemotherapeutic drug response data and clinical cohort treatment data. We first characterized and generalized phagocytosis regulators in SKCM and extensively examined the tumor immune cell infiltration. We created two phagocytosis regulator-related system (PRRS) phenotypes and derived PRRS scores using a principal component analysis (PCA) technique. We discovered that subtypes with low PRRS scores had a poor prognosis and decreased immune checkpoint-associated gene expression levels. We observed significant therapeutic and clinical improvements in patients with higher PRRS scores. Our findings imply that the PRRS scoring system can be employed as an independent and robust prognostic biomarker, serving as a critical reference point for developing novel immunotherapeutic methods.
format Online
Article
Text
id pubmed-9331497
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93314972022-07-29 The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma Xing, Jiahua Guo, Lingli Jia, Ziqi Li, Yan Han, Yan Cancers (Basel) Article SIMPLE SUMMARY: In this study, we focused on exploring phagocytosis regulators’ expression and mutational characteristics in skin cutaneous melanoma samples and delineating two molecular subtypes based on expression characteristics. We determined the relationship between phagocytosis regulators and survival by survival analysis of molecular subtypes. We then constructed a survival model (PRRS) to further quantify the criteria. Moreover, we combined pathway analysis, immune infiltration analysis, and mutation analysis to deeply explore the effects of phagocytosis regulators on skin cutaneous melanoma samples. ABSTRACT: Tumor-associated macrophages (TAMs) have gained considerable attention as therapeutic targets. Monoclonal antibody treatments directed against tumor antigens contribute significantly to cancer cell clearance by activating macrophages to phagocytose tumor cells. Due to its complicated genetic and molecular pathways, skin cutaneous melanoma (SKCM) has not yet attained the expected clinical efficacy and prognosis when compared to other skin cancers. Therefore, we chose TAMs as an entrance point. This study aimed to thoroughly assess the dysregulation and regulatory role of phagocytosis regulators in SKCM, as well as to understand their regulatory patterns in SKCM. This study subtyped prognosis-related phagocytosis regulators to investigate prognostic differences between subtypes. Then, we screened prognostic factors and constructed phagocytosis-related scoring models for survival prediction using differentially expressed genes (DEGs) between subtypes. Additionally, we investigated alternative treatment options using chemotherapeutic drug response data and clinical cohort treatment data. We first characterized and generalized phagocytosis regulators in SKCM and extensively examined the tumor immune cell infiltration. We created two phagocytosis regulator-related system (PRRS) phenotypes and derived PRRS scores using a principal component analysis (PCA) technique. We discovered that subtypes with low PRRS scores had a poor prognosis and decreased immune checkpoint-associated gene expression levels. We observed significant therapeutic and clinical improvements in patients with higher PRRS scores. Our findings imply that the PRRS scoring system can be employed as an independent and robust prognostic biomarker, serving as a critical reference point for developing novel immunotherapeutic methods. MDPI 2022-07-22 /pmc/articles/PMC9331497/ /pubmed/35892841 http://dx.doi.org/10.3390/cancers14153582 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
Xing, Jiahua
Guo, Lingli
Jia, Ziqi
Li, Yan
Han, Yan
The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title_full The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title_fullStr The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title_full_unstemmed The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title_short The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma
title_sort multi-omics landscape and clinical relevance of the immunological signature of phagocytosis regulators: implications for risk classification and frontline therapies in skin cutaneous melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331497/
https://www.ncbi.nlm.nih.gov/pubmed/35892841
http://dx.doi.org/10.3390/cancers14153582
work_keys_str_mv AT xingjiahua themultiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT guolingli themultiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT jiaziqi themultiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT liyan themultiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT hanyan themultiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT xingjiahua multiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT guolingli multiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT jiaziqi multiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT liyan multiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma
AT hanyan multiomicslandscapeandclinicalrelevanceoftheimmunologicalsignatureofphagocytosisregulatorsimplicationsforriskclassificationandfrontlinetherapiesinskincutaneousmelanoma