ArticleFunctional & integrative genomics2026
A multi-omics study integrating single-cell transcriptomics, spatial transcriptomics, and mendelian randomization unveil the implication of TRDMT1 expression in T cells on the immunotherapeutic response and prognosis in breast cancer.
Article in Functional & integrative genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
m5C, an important RNA modification, is closely associated with breast cancer; however, their causal relationship is unknown. We examined the relationship between m5C regulation and breast cancer. Genome-wide association study breast cancer data and expression quantitative trait loci of m5C regulatory factor genes in blood were collected. We explored the causal relationship among m5C regulatory genes, breast cancer susceptibility, and prognosis through Mendelian randomization. Single-cell RNA sequencing data from peripheral blood mononuclear cells of patients with breast cancer and healthy controls were used to determine the differential expression of key genes among different cellular subpopulations. The effects of these genes on specific cellular subpopulations were further explored in single-cell RNAseq data from primary breast cancer using cellular communication, metabolic and cellular function analyses and validated the findings using flow cytometry. We validated the prognostic value of specific cellular subpopulations expressing key genes and assessed the impact of antitumor immunity using spatial transcriptomics, bulk transcriptomics, and immunofluorescence analysis of tissue microarray (120 patients). Mendelian randomization analysis indicated that the expression of the m5C writer tRNA aspartate methyltransferase 1 (TRDMT1) in blood was associated with breast cancer prognosis. TRDMT1 expression in T cells was decreased in patients with breast cancer. TRDMT1 was closely related to T-cell function. Moreover, it may modulate the antitumor immune effects of CD8
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