The microenvironment cell index is a novel indicator for the prognosis and therapeutic regimen selection of cancers.

Background: It is worthwhile to establish a prognostic prediction model based on microenvironment cells (MCs) infiltration and explore new treatment strategies for triple-negative breast cancer (TNBC).
Methods: The xCell algorithm was used to quantify the cellular components of the TNBC microenvironment based on bulk RNA sequencing (bulk RNA-seq) data. The MCs index (MCI) was constructed using the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression analysis. Single-cell RNA sequencing (scRNA-seq), spatially resolved transcriptomics (SRT), and multiplex immunofluorescence (mIF) staining analyses verified MCI. The mechanism of action of the MCI was investigated in tumor-bearing mice.
Results: MCI consists of the six types of MCs, which can precisely predict the prognosis of the TNBC patients. scRNA-seq, SRT, and mIF analyses verified the existence and proportions of these cells. Furthermore, combined with the spatial distribution characteristics of the six types of MCs, an MCI-enhanced (MCI-e) model was constructed, which could predict the prognosis of the TNBC patients more accurately. More importantly, inhibition of the insulin signaling pathway activated in the cancer cells of the MCI ^high the TNBC patients significantly prolonged the survival time of tumor-bearing mice.
Conclusions: Overall, our results demonstrate that MCs infiltration can be exploited as a novel indicator for the prognosis and therapeutic regimen selection of the TNBC patients.
Competing Interests: Declarations. Ethics approval and consent to participate: All animal experimental protocols were approved by the Ethics Committee for the Use of Experimental Animals of Army Medical University (AMUWEC20227011), and all procedures were performed under governmental and institutional guidelines and regulations. The use of two TMAs derived from the TNBC patients was granted ethical approval (XYLL-2021B001), and the study was exempted from the obligation to obtain informed consent. The Declaration of Helsinki of the World Medical Association was followed when the study was conducted. Consent for publication: Written informed consent for publication was obtained from all participants. Competing interests: The authors declare that they have no competing interests.
(© 2024. The Author(s).)