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

Abstract

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.