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Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer, the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification and treatment management. Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion beam imaging that produces interpretable results, and is generalizable to other cancer types.

SUBMITTER: Patwa A

PROVIDER: S-EPMC8271023 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).MethodsThe TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.ResultsMost of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 (NSUN2) upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, NSUN6 downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between NSUN2 and NSUN6.ConclusionRegulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.

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Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer.

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