Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Abstract

Aberrant glycosylation, a post-translational modification of proteins, is regarded to engage in tumorigenesis and malignant progression of breast cancer (BC). The altered expression of glycosyltransferases causes abnormal glycan biosynthesis changes, which can serve as diagnostic hallmarks in BC. This study attempts to establish a predictive signature based on glycosyltransferase-related lncRNAs (GT-lncRNAs) in BC prognosis and response to immune checkpoint inhibitors (ICIs) treatment. We firstly screened out characterized glycosyltransferase-related genes (GTGs) through NMF and WGCNA analysis and identified GT-lncRNAs through coexpression analysis. By using the coefficients of 8 GT-lncRNAs, a risk score was calculated and its median value divided BC patients into high-and low-risk groups. The analyses unraveled that patients in the high-risk group had shorter survival and the risk score was an independent predictor of BC prognosis. Besides, the predictive efficacy of our risk score was higher than other published models. Moreover, ESTIMATE analysis, immunophenoscore (IPS), and SubMAP analysis showed that the risk score could stratify patients with distinct immune infiltration, and patients in the high-risk group might benefit more from ICIs treatment. Finally, the vitro assay showed that MIR4435-2HG might promote the proliferation and migration of BC cells, facilitate the polarization of M1 into M2 macrophages, enhance the migration of macrophages and increase the PD-1/PD-L1/CTLA4 expression. Collectively, our well-constructed prognostic signature with GT-lncRNAs had the ability to identify two subtypes with different survival state and responses to immune therapy, which will provide reliable tools for predicting BC outcomes and making rational follow-up strategies.

A DNA Replication Stress-Based Prognostic Model for Lung Adenocarcinoma

“…Tumor immune cell infiltration is tightly linked to tumor progression [ 23 ]. By analyzing the immune cell infiltration and immune-related functional pathways between the two groups, we probed the disparities in the immune activity status between the two groups ( Fig.…”

Identification of Lysine lactylation (kla) -related lncRNA signatures using XGBoost to predict prognosis and immune microenvironment in breast cancer patients

“…Suppression of MIR4435-2HG exhibits potential in hindering metastasis and invasion in BC cells via the Wnt/β-catenin pathway, indicating its candidacy as a therapeutic target [31]. RT-PCR analysis indicates that MIR4435-2HG may facilitate macrophage migration and induce M1 to M2 macrophage polarization, thereby promoting BC progression [32]. EGOT, identi ed as a BC genome instabilityassociated lncRNA, serves as a predictor for BC prognosis and immune checkpoint inhibitor e cacy [33].…”

Unveiling efferocytosis-related signatures through the integration of single-cell analysis and machine learning: a predictive framework for prognosis and immunotherapy response in hepatocellular carcinoma

“…This treatment strategy makes use of the immune system’s innate capacity to identify and get rid of cancerous cells ( 63 – 65 ). Macrophages and the crucial molecules CTLA-4, PD-1, and PD-L1 have a complex relationship ( 66 – 69 ). In order to assess the potential impact of disparate levels of macrophage infiltration on the response to immune therapy, we investigated whether such variation could influence the therapeutic efficacy ( 70 ).…”