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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
NKGD2 Ligands (NKG2DLs) in Breast Cancer: In Silico Analysis and Narrative Review
Jesús Peña-López1, Angelo Gámez-Pozo2,3, Lucía Trilla-Fuertes2
1Medical Oncology Department, Hospital Universitario La Paz, Universidad Autónoma, 28046 Madrid, Spain.
Abstract:
Breast cancer (BC) is a global health problem. BC is a biologically heterogeneous disease in which novel immunotherapeutic strategies are needed, particularly in the metastatic setting. The NKG2D/NKG2D ligand (NKG2DL) axis is a key component of innate antitumor immunity and represents a potential therapeutic target, but its relevance in BC has not been fully characterized. We performed an in silico analysis of NKG2DL expression in BC cell lines, healthy breast tissue, and tumor samples using publicly available transcriptomic databases (DSMZCellDive, ShinyTHOR, GTEx, TCGA, Human Protein Atlas), complemented by survival analyses from TCGA and KMPlot and a narrative review of the literature. NKG2DL transcripts were consistently expressed in BC cell lines and tumor tissues, with higher expression observed in ductal histology, higher tumor stage, and basal molecular subtype. Survival analyses showed heterogeneous and generally weak associations between individual NKG2DLs and clinical outcomes. In silico proteomics data are scarce, but the narrative review showed that NKG2DLs are expressed by immunohistochemistry in tumor tissues but absent in surrounding healthy tissues. The literature review also revealed concomitant dysfunction of NKG2D+ effector cells due to multiple resistance mechanisms (including ligand shedding). We also review potential therapeutic approaches.
Insights
The NKG2D/NKG2D ligand (NKG2DL) axis is expressed in breast cancer (BC) tissues, but its association with patient outcomes is weak. Resistance mechanisms may limit the effectiveness of targeting this axis in BC immunotherapy.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Breast cancer (BC) is a heterogeneous disease requiring novel immunotherapies, especially for metastatic cases.
- The NKG2D/NKG2D ligand (NKG2DL) axis is crucial for innate antitumor immunity but its role in BC is not fully understood.
Purpose of the Study:
- To investigate the expression and clinical relevance of the NKG2D/NKG2DL axis in breast cancer.
- To explore potential therapeutic strategies targeting this axis.
Main Methods:
- In silico analysis of NKG2DL expression using transcriptomic databases (e.g., GTEx, TCGA).
- Survival analyses utilizing TCGA and KMPlot data.
- Narrative literature review on NKG2DL expression and immunotherapy resistance mechanisms.
Main Results:
- NKG2DL transcripts were consistently found in BC cell lines and tumor tissues, with higher expression in ductal histology, advanced stage, and basal subtype.
- Survival analyses revealed generally weak and heterogeneous associations between individual NKG2DLs and clinical outcomes.
- Literature review indicated NKG2DL expression in tumors but not healthy tissues, alongside effector cell dysfunction and resistance mechanisms like ligand shedding.
Conclusions:
- The NKG2D/NKG2DL axis is expressed in breast cancer, but its direct correlation with prognosis is limited.
- Understanding resistance mechanisms is critical for developing effective immunotherapies targeting the NKG2D/NKG2DL pathway in BC.
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