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Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Integrated multi-omics and single-cell analysis of galectins and immune associations in triple-negative breast cancer
Peng Ji1, Hongrui Liu2, Gen-Hong Di1
1Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Background:
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies. Galectins, a family of β-galactoside-binding lectins, have emerged as important mediators of tumor-immune interactions, but their cell-type-specific expression patterns and functional roles within the tumor microenvironment of TNBC remain poorly defined.
Methods:
We integrated bulk transcriptomic and genomic data from FUSCC (n = 465) and TCGA (n = 161) TNBC cohorts with single-cell RNA sequencing data from 26 treatment-naïve patients. We systematically assessed galectin expression, genomic alterations, prognostic significance, associations with immune checkpoints and immune infiltration, and cell-type-specific patterns linked to immune contexts and therapeutic response.
Results:
Galectin family members showed broad dysregulation in TNBC, with recurrent copy number alterations contributing to transcriptional heterogeneity. At the bulk level, LGALS2 was associated with favorable survival, while LGALS3 predicted poor prognosis. Several galectins, including LGALS2, LGALS9, and LGALS10, exhibited positive correlations with immune checkpoint expression and enriched immune infiltration, particularly involving CD8⁺ T cells and tumor-infiltrating lymphocytes. Single-cell analysis revealed distinct galectin expression across malignant, immune, and stromal compartments, suggesting heterogeneous transcriptomically inferred immune contexts. Galectin expression also differed by treatment response: pathological complete response (pCR) to neoadjuvant chemo-immunotherapy was associated with higher LGALS3 and lower LGALS2, LGALS8, and LGALS9, while pCR to chemotherapy was linked to higher LGALS9 and lower LGALS1.
Conclusions:
Our study comprehensively characterizes galectin family members in TNBC, revealing their prognostic significance and association with tumor microenvironment and treatment response, and highlighting the clinical and translational relevance of galectins as candidate biomarkers and hypothesis-generating molecules for future mechanistic studies.
Insights
Galectins are dysregulated in triple-negative breast cancer (TNBC), impacting prognosis and immune interactions. This study reveals their roles in the tumor microenvironment and response to therapy, identifying potential biomarkers.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Galectins are implicated in tumor-immune interactions, but their specific roles in TNBC are unclear.
Purpose of the Study:
- To comprehensively characterize galectin expression and function in TNBC.
- To investigate galectins' association with prognosis, immune microenvironment, and treatment response.
Main Methods:
- Integrated bulk transcriptomic/genomic data (FUSCC, TCGA) with single-cell RNA sequencing.
- Assessed galectin expression, genomic alterations, prognostic value, immune checkpoint correlations, and immune infiltration.
- Analyzed cell-type-specific galectin patterns and associations with treatment response.
Main Results:
- Galectins are broadly dysregulated in TNBC, with copy number alterations contributing to heterogeneity.
- LGALS2 correlated with favorable survival, LGALS3 with poor prognosis.
- Several galectins (LGALS2, LGALS9, LGALS10) linked to immune checkpoint expression and CD8+ T cell infiltration.
- Distinct galectin expression patterns observed across malignant, immune, and stromal cells.
- Galectin profiles differed based on response to chemo-immunotherapy versus chemotherapy.
Conclusions:
- Galectins are significant in TNBC, influencing prognosis and the tumor microenvironment.
- Galectins show potential as biomarkers for predicting treatment response in TNBC.
- Further research into galectins could yield novel therapeutic strategies for TNBC.