Cargando…

Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer

Human epidermal growth factor receptor 2 (HER2) protein, which is characterized by the amplification of ERBB2, is a molecular target for HER2-overexpressing breast cancer. Many targeted HER2 strategies have been well developed thus far. Furthermore, intratumoral heterogeneity in HER2 cases has been...

Descripción completa

Detalles Bibliográficos
Autores principales: Shiino, Sho, Tokura, Momoko, Nakayama, Jun, Yoshida, Masayuki, Suto, Akihiko, Yamamoto, Yusuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527746/
https://www.ncbi.nlm.nih.gov/pubmed/37759508
http://dx.doi.org/10.3390/cells12182286
_version_ 1785111184045768704
author Shiino, Sho
Tokura, Momoko
Nakayama, Jun
Yoshida, Masayuki
Suto, Akihiko
Yamamoto, Yusuke
author_facet Shiino, Sho
Tokura, Momoko
Nakayama, Jun
Yoshida, Masayuki
Suto, Akihiko
Yamamoto, Yusuke
author_sort Shiino, Sho
collection PubMed
description Human epidermal growth factor receptor 2 (HER2) protein, which is characterized by the amplification of ERBB2, is a molecular target for HER2-overexpressing breast cancer. Many targeted HER2 strategies have been well developed thus far. Furthermore, intratumoral heterogeneity in HER2 cases has been observed with immunohistochemical staining and has been considered one of the reasons for drug resistance. Therefore, we conducted an integrated analysis of the breast cancer single-cell gene expression data for HER2-positive breast cancer cases from both scRNA-seq data from public datasets and data from our cohort and compared them with those for luminal breast cancer datasets. In our results, heterogeneous distribution of the expression of breast cancer-related genes (ESR1, PGR, ERBB2, and MKI67) was observed. Various gene expression levels differed at the single-cell level between the ERBB2-high group and ERBB2-low group. Moreover, molecular functions and ERBB2 expression levels differed between estrogen receptor (ER)-positive and ER-negative HER2 cases. Additionally, the gene expression levels of typical breast cancer-, CSC-, EMT-, and metastasis-related markers were also different across each patient. These results suggest that diversity in gene expression could occur not only in the presence of ERBB2 expression and ER status but also in the molecular characteristics of each patient.
format Online
Article
Text
id pubmed-10527746
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105277462023-09-28 Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer Shiino, Sho Tokura, Momoko Nakayama, Jun Yoshida, Masayuki Suto, Akihiko Yamamoto, Yusuke Cells Article Human epidermal growth factor receptor 2 (HER2) protein, which is characterized by the amplification of ERBB2, is a molecular target for HER2-overexpressing breast cancer. Many targeted HER2 strategies have been well developed thus far. Furthermore, intratumoral heterogeneity in HER2 cases has been observed with immunohistochemical staining and has been considered one of the reasons for drug resistance. Therefore, we conducted an integrated analysis of the breast cancer single-cell gene expression data for HER2-positive breast cancer cases from both scRNA-seq data from public datasets and data from our cohort and compared them with those for luminal breast cancer datasets. In our results, heterogeneous distribution of the expression of breast cancer-related genes (ESR1, PGR, ERBB2, and MKI67) was observed. Various gene expression levels differed at the single-cell level between the ERBB2-high group and ERBB2-low group. Moreover, molecular functions and ERBB2 expression levels differed between estrogen receptor (ER)-positive and ER-negative HER2 cases. Additionally, the gene expression levels of typical breast cancer-, CSC-, EMT-, and metastasis-related markers were also different across each patient. These results suggest that diversity in gene expression could occur not only in the presence of ERBB2 expression and ER status but also in the molecular characteristics of each patient. MDPI 2023-09-15 /pmc/articles/PMC10527746/ /pubmed/37759508 http://dx.doi.org/10.3390/cells12182286 Text en © 2023 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
Shiino, Sho
Tokura, Momoko
Nakayama, Jun
Yoshida, Masayuki
Suto, Akihiko
Yamamoto, Yusuke
Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title_full Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title_fullStr Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title_full_unstemmed Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title_short Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer
title_sort investigation of tumor heterogeneity using integrated single-cell rna sequence analysis to focus on genes related to breast cancer-, emt-, csc-, and metastasis-related markers in patients with her2-positive breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527746/
https://www.ncbi.nlm.nih.gov/pubmed/37759508
http://dx.doi.org/10.3390/cells12182286
work_keys_str_mv AT shiinosho investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer
AT tokuramomoko investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer
AT nakayamajun investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer
AT yoshidamasayuki investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer
AT sutoakihiko investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer
AT yamamotoyusuke investigationoftumorheterogeneityusingintegratedsinglecellrnasequenceanalysistofocusongenesrelatedtobreastcanceremtcscandmetastasisrelatedmarkersinpatientswithher2positivebreastcancer