scholarly journals GBP5 Serves as a Potential Marker to Predict a Favorable Response in Triple-Negative Breast Cancer Patients Receiving a Taxane-Based Chemotherapy

2021 ◽  
Vol 11 (3) ◽  
pp. 197
Author(s):  
Shun-Wen Cheng ◽  
Po-Chih Chen ◽  
Tzong-Rong Ger ◽  
Hui-Wen Chiu ◽  
Yuan-Feng Lin
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Computational Simulation ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Potential Marker ◽  
Signaling Axis

Pre-operative (neoadjuvant) or post-operative (adjuvant) taxane-based chemotherapy is still commonly used to treat patients with triple-negative breast cancer (TNBC). However, there are still no effective biomarkers used to predict the responsiveness and efficacy of taxane-based chemotherapy in TNBC patients. Here we find that guanylate-binding protein 5 (GBP5), compared to other GBPs, exhibits the strongest prognostic significance in predicting TNBC recurrence and progression. Whereas GBP5 upregulation showed no prognostic significance in non-TNBC patients, a higher GBP5 level predicted a favorable recurrence and progression-free condition in the TNBC cohort. Moreover, we found that GBP5 expression negatively correlated with the 50% inhibitory concentration (IC50) of paclitaxel in a panel of TNBC cell lines. The gene knockdown of GBP5 increased the IC50 of paclitaxel in the tested TNBC cells. In TNBC patients receiving neoadjuvant or adjuvant chemotherapy, a higher GBP5 level strongly predicted a good responsiveness. Computational simulation by the Gene Set Enrichment Analysis program and cell-based assays demonstrated that GBP5 probably enhances the cytotoxic effectiveness of paclitaxel via activating the Akt/mTOR signaling axis and suppressing autophagy formation in TNBC cells. These findings suggest that GBP5 could be a good biomarker to predict a favorable outcome in TNBC patients who decide to receive a taxane-based neoadjuvant or adjuvant therapy.

scholarly journals Expression and Prognostic Significance of Mesothelin in Her-2-Positive and Triple-Negative Breast Cancer Patients

2014 ◽  
Vol 25 ◽  
pp. iv572
Author(s):  
I.V. Bayoglu ◽  
B. Kucukzeybek ◽  
Y. Küçükzeybek ◽  
I. Yildiz ◽  
M. Akyol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Her 2

scholarly journals Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer

Oncogenesis ◽  
2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Zhen Wang ◽  
Chenghui Yang ◽  
Lili Li ◽  
Xiaoyan Jin ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
High Mobility ◽  
Underlying Mechanism ◽  
Breast Cancer Patients ◽  
Potential Marker ◽  
Novel Target

Abstract Triple-negative breast cancer (TNBC) is highly aggressive, difficult to treat and commonly develops visceral metastasis, including lung metastasis. We observed that High mobility group box 1 protein (HMGB1) was highly expressed in human TNBC and positively correlated with cancer metastasis. The hypoxic tumor environment is known to regulate HMGB1 secretion, but an understanding of the underlying mechanism by which tumor-derived HMGB1 regulates interstitial components and promotes breast cancer lung metastasis has remained elusive. The results of the present study showed that the number of CD62Ldim neutrophils, which have a strong ability to produce neutrophil extracellular traps (NETs), increased significantly in both peripheral blood and lung tissues in a mouse TNBC model and were regulated by tumor-derived HMGB1 through the TLR2 pathway. Furthermore, serum HMGB1 levels were positively correlated with CD62Ldim neutrophils in 86 breast cancer patients. We demonstrated that CD62Ldim neutrophils accelerated lung metastasis and that interventions targeting the “HMGB1-CD62Ldim neutrophil-NETs” axis could inhibit lung metastasis. Our results suggest that the combination of HMGB1 and CD62Ldim neutrophils is a potential marker for breast cancer lung metastasis and is novel target for future prevention and therapy.

scholarly journals Immune Milieu and Genomic Alterations Set the Triple-Negative Breast Cancer Immunomodulatory Subtype Tumor Behavior

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6256
Author(s):  
Rubén Rodríguez-Bautista ◽  
Claudia H. Caro-Sánchez ◽  
Paula Cabrera-Galeana ◽  
Gerardo J. Alanis-Funes ◽  
Everardo Gutierrez-Millán ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Dna Sequencing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genomic Alterations

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Seven subtypes have been described based on gene expression patterns. Herein, we characterized the tumor biology and clinical behavior of the immunomodulatory (IM) subtype. Methods: Formalin-fixed paraffin-embedded tumor samples from 68 high-risk (stage III-IV) TNBC patients were analyzed through microarrays, immunohistochemistry, and DNA sequencing. Results: The IM subtype was identified in 24% of TNBC tumor samples and characterized by a higher intratumoral (intT) and stromal (strml) infiltration of FOXP3+ TILs (Treg) compared with non-IM subtypes. Further, PD-L1+ (>1%) expression was significantly higher, as well as CTLA-4+ intT and strml expression in the IM subtype. Differential expression and gene set enrichment analysis identified biological processes associated with the immune system. Pathway analysis revealed enrichment of the β-catenin signaling pathway. The non-coding analysis led to seven Long Intergenic Non-Protein Coding RNAs (lincRNAs) (6 up-regulated and 1 down-regulated) that were associated with a favorable prognosis in the TNBC-IM subtype. The DNA sequencing highlighted two genes relevant to immune system responses: CTNNB1 (Catenin β-1) and IDH1. Conclusion: the IM subtype showed a distinct immune microenvironment, as well as subtype-specific genomic alterations. Characterizing TNBC at a molecular and transcriptomic level might guide immune-based therapy in this subgroup of patients.

scholarly journals Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ning Qing Liu ◽  
Tommaso De Marchi ◽  
Annemieke Timmermans ◽  
Anita M. A. C. Trapman-Jansen ◽  
Renée Foekens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Nuclear Expression

Prognostic significance of NLR kinetics in operable triple negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14201-e14201
Author(s):  
Ranga Raman Ganta ◽  
Srividya Nasaka
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Medical Records ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Small Sample ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Significant Difference

e14201 Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory marker, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and outcome in several malignancies. However very few reports have addressed the association of change in NLR and outcome in operable breast cancer. We evaluated preoperative NLR and postoperative NLR to assess which one would be predictive of disease outcome in triple negative breast cancer patients. Methods: This study included 67 stage I-III triple negative breast cancer patients diagnosed at HCG Cancer center, between 2013 to 2015. Those patients who underwent upfront surgery were included in the study. Patients who received neoadjuvant chemotherapy and those without adequate medical records were excluded. The NLR was calculated from the differential count by dividing neutrophil percentage with lymphocyte percentage. All preoperative NLRs were calculated from medical records, at the first visit. Postoperative NLR was obtained before first cycle chemotherapy. The NLR was divided into high if ratio is > 3 and low if it is ≤ 3. We evaluated prognostic value of NLR on 3 year DFS. Results: The median preoperative NLR was 2.52 (Range 0.77-8.6). The pre op NLR was high in 19 patients (28%) and low in 48 patients (72%). There was no significant difference between two groups in baseline characteristics. Among the preoperative High and low NLR groups, 3 year DFS is statistically significant. The median postoperative NLR was 2.23 (Range 0.89-8.1). The post operative NLR was high in 7 patients (11%) and low in 60 patients (89%). Among the postoperative High and low NLR groups, 3 year DFS is statistically not significant. The 12 (63%) patients in the high preoperative NLR patients were converted to of the low NLR after surgery. Conclusions: Preoperative NLR correlated with outcome in operable triple negative breast cancer than postoperative NLR. The NLR kinetics might be an index of response to the treatment which needs to be evaluated in prospective studies. Drawbacks of the study: single centre, retrospective study and small sample size.[Table: see text][Table: see text]

Prognostic significance of miR-34 rs4938723 T > C polymorphism in triple negative breast cancer patients

2019 ◽  
Vol 68 ◽  
pp. 9-14 ◽  
Author(s):  
Andriani Tsiakou ◽  
Flora Zagouri ◽  
Eleni Zografos ◽  
George Samelis ◽  
Maria Gazouli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Breast Cancer Patients

scholarly journals Ethnicity-Related Survival Analysis of Patients with Triple-Negative Breast Cancer

10.29007/f7fq ◽  
2019 ◽  
Author(s):  
Mohammad Owrang Ojaboni ◽  
Yasmine Kanaan ◽  
Robert Dewitty Jr
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Population Based ◽  
Lymph Node Status ◽  
Breast Cancer Patients ◽  
The Poor ◽  
Clinical Difference

Breast cancer prognostication is a vital element for providing effective treatment for breast cancer patients. Different types of breast cancer can be identified based on the existence or lack of certain receptors (i.e., estrogen, progesterone, her2 receptors). Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression. Existing studies suggest that TNBC patients tend to have worse prognosis compared to non-TNBC counterparts. The incidence of breast cancer and prognosis in women differ according to ethnicity. Given the poor prognosis of TNBC, cancer-related outcomes must be estimated accurately. Several factors responsible for the poor clinical outcomes observed in TNBC, including age, race/ethnicity, grade, tumor size, lymph node status among others, have been studied extensively. Available research data are not conclusive enough to make a convincing argument for or against a biological or clinical difference in TNBC patients based on these factors. This study was designed to investigate the effects of the ethnicity on breast cancer survivability among TNBC patients utilizing population-based Surveillance, Epidemiology, and End Results (SEER) data to confirm whether ethnicity factor has prognostic significance.

scholarly journals PSMB5 is associated with proliferation and drug resistance in triple-negative breast cancer

2017 ◽  
Vol 33 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Wensong Wei ◽  
Yufeng Zou ◽  
Qihua Jiang ◽  
Zhibin Zhou ◽  
Haolong Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Functional Module ◽  
Enrichment Analysis ◽  
Chemotherapeutic Agents ◽  
Gene Set Enrichment Analysis ◽  
Disease Stage ◽  
Cancer Subtypes

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can’t benefit fully from currently available targeted therapies. Methods: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. Results: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. Conclusions: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.

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