The analysis of plasma proteomics for luminal A breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Meimei Zhao
PROVIDER: PXD074130 | iProX | Fri Feb 06 00:00:00 GMT 2026
REPOSITORIES: iProX
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Project description:Breast cancer (BC) is the second most common type of cancer in women and one of the leading causes of cancer-related deaths worldwide. BC classification is based on the detection of three main histological markers: estrogen receptor alpha (ERα), progesterone receptor (PR) and the amplification of epidermal growth factor receptor 2 (HER2/neu). A specific BC subtype, named triple-negative BC (TNBC), lacks the aforementioned markers but a fraction of them express the estrogen receptor beta (ERβ). To investigate the functional role of ERβ in these tumors, interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors partners in MDA-MD-468 and HCC1806 TNBC cells.
2019-12-03 | PXD014468 | Pride
Project description:Purpose In breast cancer, specific aberrant methylation patterns have been associated with different BC histologic and molecular subtypes and data suggest that DNA methylation profiles may play an important role in the development and progression of distinct breast subtypes. However, the epigenome of the newly defined luminal B and luminal B-HER2 positive breast cancers has not yet been characterized. Therefore the main goal of the current study is to deciphered the aberrant DNA methylation profiles associated with these breast cancer subtypes. Experimental Design 29 luminal subtype breast cancer samples along with 8 control tissue were epigenetically interrogated using the HumanMethylation27 DNA Analysis BeadChip. Results Luminal B-HER2 + subtype displays the most aggressive phenotype and shows the highest number of aberrantly methylated CpG markers. On the other hand, the luminal B subtype harbours an heterogeneous DNA methylation profile that seems to be half way between the luminal A and luminalB-HER2+ subtypes. Conclusions The heterogeneous epigenetic and genetic profile of the luminal B subtype, might indicate that a further stratification has to be done for this specific breast cancer subtype.
2016-12-18 | GSE73808 | GEO
Project description:Dysregulated lipid metabolism promotes the progression of various cancers, including breast cancer. This study aimed to explore the lipidomic profiles of breast cancer patients, providing insights into the correlation between lipid compositions and tumor subtypes characterized by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Briefly, 30 breast cancer patients were categorized into four cohorts based on their HR and HER2 status: HR+, HER2 zero (HR+ HER2-0); HR+, HER2 low (HR+ HER2-low); HR+, HER2 pos (HR+ HER2-pos); and HR-, HER2 positive (HR- HER2-pos). Lipidomic profiles were analyzed using high-throughput liquid chromatography-mass spectrometry (LC-MS). Data were processed through principal component analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Random Forest (RF) classification to assess lipidomic variations and significant lipid features among these groups. Profiles of lipids, particularly triglycerides (TG) such as TG (16:0_18:1_18:1) +NH4, were significantly different across the cohorts. PCA and PLS-DA analyses identified unique lipid profiles in the HR+ HER2-pos and HR+ HER2-0 groups, while RF highlighted PIP3(21:2)+NH4 as a crucial lipid feature for accurate patient grouping. Advanced statistical analysis showed significant correlations between lipid carbon chain length and the number of double bonds with the classifications, providing insights into the role of structural lipid properties in tumor biology. Additionally, a clustering heatmap and network analysis indicated significant lipid-lipid interactions. Pathway enrichment analysis showed critical biological pathways, such as the assembly of active LPL and LIPC lipase complexes. In conclusion, the study underscores the importance of lipidomic profiling is crucial in understanding the metabolic alterations associated with different breast cancer subtypes. These findings highlight specific lipid features and interactions that may serve as potential biomarkers for breast cancer classification and target pathways for therapeutic intervention. Furthermore, advanced lipidomic analyses can be integrated to decipher complex biological data, offering a foundation for further research into the role of lipid metabolism in cancer progression.
2024-08-16 | MTBLS10858 | MetaboLights
Project description:Genome wide DNA methylation profiling of non-tumoral and infiltrating ductal breast cancer (tumoral) samples. The HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpG in non-tumoral and tumoral samples. Non-tumoral samples included six frozen non-neoplastic breast tissues from reduction mammoplasties and tumoral samples included eight frozen tumors from each BC subtype, i.e. luminal A (LA), luminal B (LB), luminal-HER2 (LH), HER2 (H) and triple-negative (TN) (Total: 40 tumors).
2020-02-17 | GSE141338 | GEO
Project description:Growth arrest and DNA damage-inducible alpha (GADD45A) has context-dependent roles in cancer, yet its function in hormone receptor-positive (HR+) breast cancer remains poorly defined. We characterized GADD45A across breast cancer subtypes and investigated its prognostic significance and connection to estrogen and Hippo-TEAD signaling in HR+HER2− breast cancer. GADD45A protein expression was evaluated by immunohistochemistry in 100 tissue microarray samples and 16 CDK4/6 inhibitor-treated metastatic cases. Prognostic associations were assessed in the METABRIC (n = 1,904) and TCGA-BRCA cohorts. siRNA-mediated GADD45A knockdown was performed in MCF7 and T47D cells followed by RNA sequencing and integration with TEAD4 ChIP-seq data. GADD45A protein was preferentially expressed in HR+HER2− tumors and correlated with estrogen receptor levels. High GADD45A expression was associated with improved overall and relapse-free survival in HR+HER2− breast cancer but not in other subtypes. GADD45A knockdown led to downregulation of estrogen response and Hippo-TEAD positive effector programs with concurrent upregulation of E2F targets and cell cycle pathways. Integration with TEAD4 ChIP-seq data demonstrated significant enrichment of TEAD4 promoter binding among GADD45A-regulated genes, including Hippo-TEAD components, chromatin remodeling machinery, and luminal identity regulators. GADD45A is a subtype-specific prognostic marker in HR+HER2− breast cancer that sustains estrogen-responsive and TEAD-mediated transcriptional programs, identifying it as a previously unrecognized link between Hippo-TEAD signaling and luminal gene maintenance.
2026-03-09 | GSE323399 | GEO
Project description:Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the most common type of breast cancer, is facing challenges such as endocrine therapy resistance and distant relapse. Immunotherapy has shown progress in treating triple-negative breast cancer, but immunological research on HR+/HER2- breast cancer is still in its early stages. Here, we performed a multi-omics analysis of a large cohort of HR+/HER2- breast cancer patients (n = 351) and revealed that HR+/HER2- breast cancer possessed a highly heterogeneous tumor immune microenvironment. Notably, the immunological heterogeneity of HR+/HER2- breast cancer was related to MAP3K1 mutation and we validated experimentally that MAP3K1 mutation could attenuate CD8+ T cell-mediated antitumor immunity. Mechanistically, MAP3K1 mutation suppressed MHC-I-mediated tumor antigen presentation through promoting the degradation of antigen peptide transporter 1/2 (TAP1/2) mRNAs, thereby driving tumor immune escape. In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy.
2024-12-20 | GSE276527 | GEO
Project description:We performed high throughput transcriptome of breast cancer and normal tissues, identifying lincRNA associated molecular subtype with powerful capacity to distinct breast cancer population and predict prognosis. We also identified subtype-specific lincRNAs that may be a useful complement to intrinsic molecular subtype classification when divergence emerges among pathologists.Paired-end transcriptome sequencing were carried out on a cohort of 33 breast tissues from 11 groups including five breast cancer subtypes including luminal A (LA), luminal B (HER2 negative)(LB, HER2-), luminal B (HER2 positive) (LB, HER2+), HER2 and tripple negative breast cancer (TNB), adjacent noncancerous breast tissue (ANT, three samples for each subtype) and the complete normal breast tissues (three samples)
2017-09-06 | GSE71651 | GEO
Project description:Introduction In HR+/HER2- metastatic breast cancer (MBC) is imperative to identify patients who respond poorly to CDK4/6i and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting but further validation is needed. Methods We performed mRNA gene expression profiling and correlation with progression-free-survival (PFS) on 455 tumor samples included in the phase III PEARL study, that assigned HR+/HER2- MBC patients to receive palbociclib+ET vs capecitabine. ER+/HER2- breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET. Results Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4months (m) with palbociclib+ET and 9.3m with capecitabine; HR:4.16, adjusted p-value<0.0001. Tumors with high CCNE1 expression (above median) had also worse median PFS with palbociclib+ET (6.2m) than with capecitabine (9.3m); HR:1.55, adjusted p-value=0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile) we found higher levels of Polo Like Kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2- cell line models we show that PLK1 inhibition reverses resistance to palbociclib+ET. Conclusion We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i.
2023-01-26 | GSE223700 | GEO
Project description:Resistance to CDK4/6 inhibitors leads to treatment failure and disease progression in women with HR+HER2- breast cancer (BC). We delineated a hypoxia-sensitive, CCL2-dependent pathway recruiting IL17A-secreting γδ T cells to mouse HR+HER2- BCs upon CDK4/6 inhibition, resulting in repolarization of tumor-associated macrophages (TAMs) towards an immunosuppressive CX3CR1+ phenotype associated with resistance. Increased IL17A signaling and intratumoral γδ T cell abundance positively correlated with advanced grade and/or reduced survival in two cohorts of HR+HER2- BC patients. Circulating γδ T cells and plasma CCL2 levels negatively correlated with progression in an independent series of patients with HR+HER2- BC receiving CDK4/6 inhibitors. Intratumoral γδ T cells were increased in post- vs pre-treatment biopsies from HR+HER2- BC patients relapsing on CDK4/6 inhibitors. CX3CR1+ TAMs had negative prognostic impact in women with HR+HER2- BC receiving neoadjuvant PD-1 blockage and radiotherapy. Thus, γδ T cells and CX3XR1+ TAMs may favor resistance to CDK4/6 inhibitors in HR+HER2- BC patients.
2025-05-09 | GSE296805 | GEO
Project description:Resistance to CDK4/6 inhibitors leads to treatment failure and disease progression in women with HR+HER2- breast cancer (BC). We delineated a hypoxia-sensitive, CCL2-dependent pathway recruiting IL17A-secreting γδ T cells to mouse HR+HER2- BCs upon CDK4/6 inhibition, resulting in repolarization of tumor-associated macrophages (TAMs) towards an immunosuppressive CX3CR1+ phenotype associated with resistance. Increased IL17A signaling and intratumoral γδ T cell abundance positively correlated with advanced grade and/or reduced survival in two cohorts of HR+HER2- BC patients. Circulating γδ T cells and plasma CCL2 levels negatively correlated with progression in an independent series of patients with HR+HER2- BC receiving CDK4/6 inhibitors. Intratumoral γδ T cells were increased in post- vs pre-treatment biopsies from HR+HER2- BC patients relapsing on CDK4/6 inhibitors. CX3CR1+ TAMs had negative prognostic impact in women with HR+HER2- BC receiving neoadjuvant PD-1 blockage and radiotherapy. Thus, γδ T cells and CX3XR1+ TAMs may favor resistance to CDK4/6 inhibitors in HR+HER2- BC patients.
2025-05-09 | GSE296798 | GEO