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Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer

BACKGROUND: Despite the consistency of patient age, disease stage and treatment options, the prognosis of different high-grade serous ovarian carcinoma (HGSOC) patients is different. Here, we sought to measure predictive biomarkers for distinct responses to platinum-based chemotherapy and immunother...

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Autores principales: Yang, Hua, Yu, Mei, Zhong, Sen, You, Yan, Feng, Fengzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801100/
https://www.ncbi.nlm.nih.gov/pubmed/35093146
http://dx.doi.org/10.1186/s13048-022-00955-9
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author Yang, Hua
Yu, Mei
Zhong, Sen
You, Yan
Feng, Fengzhi
author_facet Yang, Hua
Yu, Mei
Zhong, Sen
You, Yan
Feng, Fengzhi
author_sort Yang, Hua
collection PubMed
description BACKGROUND: Despite the consistency of patient age, disease stage and treatment options, the prognosis of different high-grade serous ovarian carcinoma (HGSOC) patients is different. Here, we sought to measure predictive biomarkers for distinct responses to platinum-based chemotherapy and immunotherapy benefits. METHODS: Sixteen HGSOC patients receiving debulking surgery and adjuvant first-line combination chemotherapy at Peking Union Medical College Hospital (PUMCH) were enrolled. Whole exome sequencing (WES) and RNA-seq were performed on tumor and normal tissues of these patients. RESULTS: The tumor mutational burden (TMB) and intratumoral heterogeneity (ITH) of the platinum-resistant group were significantly higher than those of the platinum-sensitive group (P=0.0321 and P=0.0452, respectively). TMB, neoantigen and ITH had certain predictive value according to the area under the receiver operating characteristic (ROC) curve (AUC 0.7778 for TMB, 0.7619 for neoantigen, 0.7778 for ITH). The infiltration of other immune cells in tumor tissues was different between the two groups, but the difference was not significant. Univariate Cox proportional hazard analysis revealed poorer progression-free survival (PFS) for those patients who carried a higher number of neoantigens (P =0.0069), higher TMB (P =0.0083), and higher ITH (P =0.0249). Further Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis indicated the Differentially expressed genes (DEGs) in platinum-resistant and platinum-sensitive patients were mainly enriched in the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway and focal adhesion pathway, which are associated with platinum resistance. CONCLUSIONS: Higher TMB, neoantigen and ITH may account for the worse prognosis of patients with platinum-based chemotherapy and higher TMB was observed in the platinum-resistant group, which could make the patients in the platinum-resistant group to be the better candidates for immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-00955-9.
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spelling pubmed-88011002022-02-02 Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer Yang, Hua Yu, Mei Zhong, Sen You, Yan Feng, Fengzhi J Ovarian Res Research BACKGROUND: Despite the consistency of patient age, disease stage and treatment options, the prognosis of different high-grade serous ovarian carcinoma (HGSOC) patients is different. Here, we sought to measure predictive biomarkers for distinct responses to platinum-based chemotherapy and immunotherapy benefits. METHODS: Sixteen HGSOC patients receiving debulking surgery and adjuvant first-line combination chemotherapy at Peking Union Medical College Hospital (PUMCH) were enrolled. Whole exome sequencing (WES) and RNA-seq were performed on tumor and normal tissues of these patients. RESULTS: The tumor mutational burden (TMB) and intratumoral heterogeneity (ITH) of the platinum-resistant group were significantly higher than those of the platinum-sensitive group (P=0.0321 and P=0.0452, respectively). TMB, neoantigen and ITH had certain predictive value according to the area under the receiver operating characteristic (ROC) curve (AUC 0.7778 for TMB, 0.7619 for neoantigen, 0.7778 for ITH). The infiltration of other immune cells in tumor tissues was different between the two groups, but the difference was not significant. Univariate Cox proportional hazard analysis revealed poorer progression-free survival (PFS) for those patients who carried a higher number of neoantigens (P =0.0069), higher TMB (P =0.0083), and higher ITH (P =0.0249). Further Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis indicated the Differentially expressed genes (DEGs) in platinum-resistant and platinum-sensitive patients were mainly enriched in the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway and focal adhesion pathway, which are associated with platinum resistance. CONCLUSIONS: Higher TMB, neoantigen and ITH may account for the worse prognosis of patients with platinum-based chemotherapy and higher TMB was observed in the platinum-resistant group, which could make the patients in the platinum-resistant group to be the better candidates for immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-00955-9. BioMed Central 2022-01-29 /pmc/articles/PMC8801100/ /pubmed/35093146 http://dx.doi.org/10.1186/s13048-022-00955-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Hua
Yu, Mei
Zhong, Sen
You, Yan
Feng, Fengzhi
Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title_full Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title_fullStr Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title_full_unstemmed Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title_short Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
title_sort neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801100/
https://www.ncbi.nlm.nih.gov/pubmed/35093146
http://dx.doi.org/10.1186/s13048-022-00955-9
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