Cargando…

Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esoph...

Descripción completa

Detalles Bibliográficos
Autores principales: Pang, Jingjing, Pan, He, Yang, Chunxiu, Meng, Pei, Xie, Wen, Li, Jiahao, Li, Yueying, Xiao, Shu-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516150/
https://www.ncbi.nlm.nih.gov/pubmed/34659345
http://dx.doi.org/10.3389/fgene.2021.722601
_version_ 1784583741612490752
author Pang, Jingjing
Pan, He
Yang, Chunxiu
Meng, Pei
Xie, Wen
Li, Jiahao
Li, Yueying
Xiao, Shu-Yuan
author_facet Pang, Jingjing
Pan, He
Yang, Chunxiu
Meng, Pei
Xie, Wen
Li, Jiahao
Li, Yueying
Xiao, Shu-Yuan
author_sort Pang, Jingjing
collection PubMed
description Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Bioinformatic analyses were conducted based on the RNA-seq, genomic mutation, and clinical data from TCGA and GEO cohorts. We clustered patients into high-immunity and low-immunity groups through the ssGSEA results. The ESTIMATE algorithm was used to evaluate the tumor microenvironment. Patients with high immunity in both ESCC and EAC had lower tumor purity and poor survival. Subsequently, CIBERSORT was performed to learn about the detailed difference of tumor-infiltrating lymphocytes (TILs) between high- and low-immunity patients. Specific increase of M2 macrophages and decrease of activated dendric cells can be observed in ESCC and EAC, respectively. The most enriched functions and pathways of high-immunity patients were immunoglobulin complex, MHC class II protein complex, and allograft rejection according to the GO terms and KEGG. Two prognostic immune-related multi-lncRNA risk models were constructed and validated by ROC curve and PCA in ESCC and EAC. High-risk patients in both subtypes had poor survival, advanced clinical characteristics, and higher drug susceptibility except cisplatin and sorafenib. In addition, the tumor mutation burden (TMB) was positively correlated with the risk level in the ESCC and EAC and showed distinct differences between the two subtypes. In summary, we comprehensively analyzed the tumor microenvironment for two subtypes of esophageal cancer, identified two multi-lncRNA signatures predictive for the prognosis, and explored the possibility of the signatures to forecast drug susceptibility as well as TMB for the first time. The findings may serve as a conceptual basis for innovative strategy of individualized immunotherapy for esophageal cancer.
format Online
Article
Text
id pubmed-8516150
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85161502021-10-15 Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer Pang, Jingjing Pan, He Yang, Chunxiu Meng, Pei Xie, Wen Li, Jiahao Li, Yueying Xiao, Shu-Yuan Front Genet Genetics Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Bioinformatic analyses were conducted based on the RNA-seq, genomic mutation, and clinical data from TCGA and GEO cohorts. We clustered patients into high-immunity and low-immunity groups through the ssGSEA results. The ESTIMATE algorithm was used to evaluate the tumor microenvironment. Patients with high immunity in both ESCC and EAC had lower tumor purity and poor survival. Subsequently, CIBERSORT was performed to learn about the detailed difference of tumor-infiltrating lymphocytes (TILs) between high- and low-immunity patients. Specific increase of M2 macrophages and decrease of activated dendric cells can be observed in ESCC and EAC, respectively. The most enriched functions and pathways of high-immunity patients were immunoglobulin complex, MHC class II protein complex, and allograft rejection according to the GO terms and KEGG. Two prognostic immune-related multi-lncRNA risk models were constructed and validated by ROC curve and PCA in ESCC and EAC. High-risk patients in both subtypes had poor survival, advanced clinical characteristics, and higher drug susceptibility except cisplatin and sorafenib. In addition, the tumor mutation burden (TMB) was positively correlated with the risk level in the ESCC and EAC and showed distinct differences between the two subtypes. In summary, we comprehensively analyzed the tumor microenvironment for two subtypes of esophageal cancer, identified two multi-lncRNA signatures predictive for the prognosis, and explored the possibility of the signatures to forecast drug susceptibility as well as TMB for the first time. The findings may serve as a conceptual basis for innovative strategy of individualized immunotherapy for esophageal cancer. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8516150/ /pubmed/34659345 http://dx.doi.org/10.3389/fgene.2021.722601 Text en Copyright © 2021 Pang, Pan, Yang, Meng, Xie, Li, Li and Xiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Pang, Jingjing
Pan, He
Yang, Chunxiu
Meng, Pei
Xie, Wen
Li, Jiahao
Li, Yueying
Xiao, Shu-Yuan
Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title_full Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title_fullStr Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title_full_unstemmed Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title_short Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer
title_sort prognostic value of immune-related multi-incrna signatures associated with tumor microenvironment in esophageal cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516150/
https://www.ncbi.nlm.nih.gov/pubmed/34659345
http://dx.doi.org/10.3389/fgene.2021.722601
work_keys_str_mv AT pangjingjing prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT panhe prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT yangchunxiu prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT mengpei prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT xiewen prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT lijiahao prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT liyueying prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer
AT xiaoshuyuan prognosticvalueofimmunerelatedmultiincrnasignaturesassociatedwithtumormicroenvironmentinesophagealcancer