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Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level

BACKGROUND: Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the d...

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Autores principales: Zhang, Yan, Zhang, Denan, Meng, Qingkang, Liu, Ziqi, Xie, Hongbo, Liu, Lei, Xu, Fei, Chen, Xiujie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361656/
https://www.ncbi.nlm.nih.gov/pubmed/34388989
http://dx.doi.org/10.1186/s12885-021-08617-7
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author Zhang, Yan
Zhang, Denan
Meng, Qingkang
Liu, Ziqi
Xie, Hongbo
Liu, Lei
Xu, Fei
Chen, Xiujie
author_facet Zhang, Yan
Zhang, Denan
Meng, Qingkang
Liu, Ziqi
Xie, Hongbo
Liu, Lei
Xu, Fei
Chen, Xiujie
author_sort Zhang, Yan
collection PubMed
description BACKGROUND: Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method. METHODS: Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients. RESULTS: Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes. CONCLUSIONS: For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08617-7.
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spelling pubmed-83616562021-08-17 Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level Zhang, Yan Zhang, Denan Meng, Qingkang Liu, Ziqi Xie, Hongbo Liu, Lei Xu, Fei Chen, Xiujie BMC Cancer Research BACKGROUND: Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method. METHODS: Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients. RESULTS: Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes. CONCLUSIONS: For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08617-7. BioMed Central 2021-08-13 /pmc/articles/PMC8361656/ /pubmed/34388989 http://dx.doi.org/10.1186/s12885-021-08617-7 Text en © The Author(s) 2021 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
Zhang, Yan
Zhang, Denan
Meng, Qingkang
Liu, Ziqi
Xie, Hongbo
Liu, Lei
Xu, Fei
Chen, Xiujie
Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title_full Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title_fullStr Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title_full_unstemmed Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title_short Precision treatment exploration of breast cancer based on heterogeneity analysis of lncRNAs at the single-cell level
title_sort precision treatment exploration of breast cancer based on heterogeneity analysis of lncrnas at the single-cell level
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361656/
https://www.ncbi.nlm.nih.gov/pubmed/34388989
http://dx.doi.org/10.1186/s12885-021-08617-7
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