Combined mRNAs and clinical factors model on predicting prognosis in patients with triple-negative breast cancer

Objective Triple-negative breast cancer (TNBC) is aggressive cancer usually diagnosed in young women with no effective prognosis prediction model to use. The present study was performed to develop a useful prognostic model for predicting overall survival (OS) for TNBC patients. Methods The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used as training and validation data sets, respectively, in which the gene expression levels and clinical prognostic information of TNBC were collected. Differentially expressed genes (DEGs) between TNBC and non-TNBC (NTNBC) were identified with the thresholds of false discovery rate < 0.05 and |log2 Fold Change| > 1. DEGs in AmiGO2 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were retained for further study. Univariate, multivariate Cox, and logistic regression analysis were conducted for detecting DEG signature with the threshold of log-rank P < 0.05. The prognosis models of mRNA signature, clinical factors were constructed and compared. Results One five-DEG signature, including CHST4, COCH, CST9, SOX11, and TDGF1 was identified in DEG prognosis model. Stratified analysis showed that the patients aged over 60, with higher pathologic stage (III-IV) and recurrence induced a significantly lower survival rate than those aged below 60, lower pathologic stage and without recurrence. Compared with patients with low-risk scores, those presented high-risk scores demonstrated significantly lower survival rate in the subgroup aged over 60 [HR = 3.780 (1.801–7.933), P < 0.0001]. For patients who obtained a higher pathologic stage and recurrence, high-risk scores were correlated with a significantly lower survival rate than patients with low-risk scores. The five-mRNA signature combined with clinical model (AUC = 0.950) predicted better than single clinical model (AUC = 0.795) or five-mRNA signature model (AUC = 0.823). Conclusion Our present study identified a prognostic prediction model (combined with five-mRNA signature and clinical factors) for TNBC patients receiving immunotherapy, which will benefit future research and clinical therapies.

Download Full-text

Black women’s lower survival rate for breast cancer not due to differences in treatment

Nursing Standard ◽

10.7748/ns2013.09.28.2.15.s22 ◽

2013 ◽

Vol 28 (2) ◽

pp. 15-15

Keyword(s):

Breast Cancer ◽

Survival Rate ◽

Lower Survival Rate ◽

Lower Survival

Download Full-text

HBx enhances CPAP expression via interacting with CREB to promote hepatocarcinogenesis in HBV-associated HCC

10.1101/423194 ◽

2018 ◽

Author(s):

Chia-Jui Yen ◽

Shu-Ting Yang ◽

Ruo-Yu Chen ◽

Wenya Huang ◽

Kazuaki Chayama ◽

...

Keyword(s):

Cell Proliferation ◽

Survival Rate ◽

High Risk ◽

Protein Stability ◽

Risk Group ◽

High Risk Group ◽

Hbv Infection ◽

Dependent Manner ◽

Lower Survival Rate ◽

Lower Survival

AbstractHepatitis B virus (HBV) encoded non-structure protein X (HBx) can promote cell proliferation, migration, and anti-apoptosis via activating several transcription factors and increasing their downstream gene expression in HBV-infected liver cells. Our previous report suggested that centrosomal P4.1-associated protein (CPAP) is required for HBx-mediated NF-κB activation. Here, we found that, upon HBV infection, overexpressed HBx can transcriptionally up-regulateCPAPvia interacting with CREB. CPAP can directly interact with HBx to promote HBx-mediated cell proliferation and migration; and SUMO modification of CPAP is involved in interacting with HBx. Interestingly, CPAP can increase the HBx protein stability in an NF-κB-dependent manner; and overexpressed CPAP and HBx is positively correlated with the activation status of NF-κB in HCC. Increased expression ofCREBandCPAPmRNAs exists in the high-risk group with a lower survival rate in hepatocellular carcinoma (HCC). These results suggest that the reciprocal regulation between CPAP and HBx may provide a microenvironment to facilitate HCC development via enhancing NF-κB activation, inflammatory cytokine production, and cancer maligancies. The findings of this study not only shed light on the role of CPAP in HBV-associated HCC, but also provide CPAP as a potential target for HBV-related HCC therapy.Author SummaryIn this study, we address a novel molecular mechanism for the collaboration between overexpressed HBx and CPAP in promoting hepatocarcinogenesis in HBV-associated HCC. Upon HBV infection, HBx is overexpressed and interacts with CREB to transcriptionally activate CPAP; the HBx/CPAP interaction promotes hepatocarcinogenesis. Clinical analysis found that co-overexpressed CPAP and CREB exist in the high-risk group with a lower survival rate in HCC. Additionally, overexpressed CPAP contributes to HBx protein stability in a NF-κB-dependent pathway. Our study provides a potential translational application in targeting CREB-CPAP axis in HBV-associated HCC.

Download Full-text

Gender differences in abdominal aortic aneurysm therapy – a systematic review

VASA ◽

10.1024/0301-1526/a000703 ◽

2018 ◽

Vol 47 (4) ◽

pp. 267-272 ◽

Cited By ~ 9

Author(s):

Konstanze Stoberock ◽

Tilo Kölbel ◽

Gülsen Atlihan ◽

Eike Sebastian Debus ◽

Nikolaos Tsilimparis ◽

...

Keyword(s):

Gender Differences ◽

Abdominal Aortic Aneurysm ◽

Survival Rate ◽

Aortic Aneurysm ◽

Endovascular Treatment ◽

Aortic Aneurysms ◽

Lower Survival Rate ◽

Lower Survival ◽

Abdominal Aortic ◽

Risk Of Rupture

Abstract. This article analyses if and to what extent gender differences exist in abdominal aortic aneurysm (AAA) therapy. For this purpose Medline (PubMed) was searched from January 1999 to January 2018. Keywords were: “abdominal aortic aneurysm”, “gender”, “prevalence”, “EVAR”, and “open surgery of abdominal aortic aneurysm”. Regardless of open or endovascular treatment of abdominal aortic aneurysms, women have a higher rate of complications and longer hospitalizations compared to men. The majority of studies showed that women have a lower survival rate for surgical and endovascular treatment of abdominal aneurysms after both elective and emergency interventions. Women receive less surgical/interventional and protective medical treatment. Women seem to have a higher risk of rupture, a lower survival rate in AAA, and a higher rate of complications, regardless of endovascular or open treatment. The gender differences may be due to a higher age of women at diagnosis and therapy associated with higher comorbidity, but also because of genetic, hormonal, anatomical, biological, and socio-cultural differences. Strategies for treatment in female patients must be further defined to optimize outcome.

Download Full-text

Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00240-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Maitri Kalra ◽

Yan Tong ◽

David R. Jones ◽

Tom Walsh ◽

Michael A. Danso ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Neoadjuvant Therapy ◽

Triple Negative ◽

Residual Disease ◽

Disease Free Survival ◽

Parp Inhibition ◽

High Risk Population ◽

Risk Population ◽

The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

Download Full-text

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

Nano Research ◽

10.1007/s12274-021-3507-8 ◽

2021 ◽

Author(s):

Alessia Felici ◽

Daniele Di Mascolo ◽

Miguel Ferreira ◽

Simone Lauciello ◽

Luca Bono ◽

...

Keyword(s):

Breast Cancer ◽

Survival Rate ◽

Triple Negative Breast Cancer ◽

Near Infrared ◽

Triple Negative ◽

Tumor Regression ◽

Polymer Mixture ◽

Poly Vinyl Alcohol ◽

Glycol Diacrylate ◽

Breast Cancer Growth

AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting “multi-passage” DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional “single-passage” approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.

Download Full-text

Radiotherapy Can Improve the Disease‐Free Survival Rate in Triple‐Negative Breast Cancer Patients with T1–T2 Disease and One to Three Positive Lymph Nodes After Mastectomy

The Oncologist ◽

10.1634/theoncologist.2012-0233 ◽

2013 ◽

Vol 18 (2) ◽

pp. 141-147 ◽

Cited By ~ 16

Author(s):

Xingxing Chen ◽

Xiaoli Yu ◽

Jiayi Chen ◽

Zhaozhi Yang ◽

Zhimin Shao ◽

...

Keyword(s):

Breast Cancer ◽

Survival Rate ◽

Cancer Patients ◽

Triple Negative ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Disease Free Survival Rate ◽

Disease Free ◽

Positive Lymph Nodes

Download Full-text

Critical Analysis of Genome-Wide Association Studies: Triple Negative Breast Cancer Quae Exempli Causa

International Journal of Molecular Sciences ◽

10.3390/ijms21165835 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5835

Author(s):

Maria-Ancuta Jurj ◽

Mihail Buse ◽

Alina-Andreea Zimta ◽

Angelo Paradiso ◽

Schuyler S. Korban ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Genetic Risk ◽

Triple Negative ◽

Cancer Susceptibility ◽

Association Studies ◽

Breast Cancer Susceptibility ◽

Risk Scores ◽

Genome Wide Association Studies ◽

Genome Wide

Genome-wide association studies (GWAS) are useful in assessing and analyzing either differences or variations in DNA sequences across the human genome to detect genetic risk factors of diseases prevalent within a target population under study. The ultimate goal of GWAS is to predict either disease risk or disease progression by identifying genetic risk factors. These risk factors will define the biological basis of disease susceptibility for the purposes of developing innovative, preventative, and therapeutic strategies. As single nucleotide polymorphisms (SNPs) are often used in GWAS, their relevance for triple negative breast cancer (TNBC) will be assessed in this review. Furthermore, as there are different levels and patterns of linkage disequilibrium (LD) present within different human subpopulations, a plausible strategy to evaluate known SNPs associated with incidence of breast cancer in ethnically different patient cohorts will be presented and discussed. Additionally, a description of GWAS for TNBC will be presented, involving various identified SNPs correlated with miRNA sites to determine their efficacies on either prognosis or progression of TNBC in patients. Although GWAS have identified multiple common breast cancer susceptibility variants that individually would result in minor risks, it is their combined effects that would likely result in major risks. Thus, one approach to quantify synergistic effects of such common variants is to utilize polygenic risk scores. Therefore, studies utilizing predictive risk scores (PRSs) based on known breast cancer susceptibility SNPs will be evaluated. Such PRSs are potentially useful in improving stratification for screening, particularly when combining family history, other risk factors, and risk prediction models. In conclusion, although interpretation of the results from GWAS remains a challenge, the use of SNPs associated with TNBC may elucidate and better contextualize these studies.

Download Full-text