scholarly journals Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chuanwei Yang ◽  
Xuemei Zhao ◽  
Naipeng Cui ◽  
Yulong Liang
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Transcription Factors ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
The Cancer Genome Atlas ◽  
Stem Cell Regulation ◽  
Luminal Type ◽  
Cancer Genome Atlas ◽  
Map Analysis

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9. CDH2/4/6/17-enriched genes including FOXM1 and MCM2 were also clustered and regulated by NFY (nuclear transcription factor Y) and/or EVI1/MECOM. Meanwhile, these SC-TFs including NFYA were upregulated in TNBC cells, but they were downregulated in luminal type of cells. Furthermore, small compounds might be predicted via the Connectivity Map analysis to target TNBC with the alterations of CDH2/4/6/17 and SC-TFs. Together with the important role of these SC-TFs in the stem cell regulation, our data provide novel insights into the maintenance of CSCs in TNBC and the discovery of these SC-TFs associated with the alterations of CDH2/4/6/17 has an implication in targeted therapy of TNBC.

scholarly journals Characterization of ceRNA network to reveal potential prognostic biomarkers in triple-negative breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7522 ◽  
Author(s):  
Xiang Song ◽  
Chao Zhang ◽  
Zhaoyun Liu ◽  
Qi Liu ◽  
Kewen He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Quantitative Polymerase Chain Reaction ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Non Coding Rnas

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan–Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.

scholarly journals Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer

2021 ◽  
pp. 1777-1787
Author(s):  
Katharine A. Collier ◽  
Sarah Asad ◽  
David Tallman ◽  
Janet Jenison ◽  
Andrei Rajkovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Copy Number ◽  
Triple Negative ◽  
Molecular Taxonomy ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Cancer Genome Atlas ◽  
Platinum Chemotherapy ◽  
Somatic Copy Number Alterations

PURPOSE To determine whether specific somatic copy-number alterations detectable in circulating tumor DNA (ctDNA) from patients with metastatic triple-negative breast cancer (mTNBC) are associated with sensitivity to platinum chemotherapy. MATERIALS AND METHODS In this secondary analysis of a large cohort of patients with mTNBC whose ctDNA underwent ultralow-pass whole-genome sequencing, tumor fraction and somatic copy-number alterations were derived with the ichorCNA algorithm. Seventy-two patients were identified who had received a platinum-based chemotherapy regimen in the metastatic setting. Gene-level copy-number analyses were performed with GISTIC2.0. Cytobands were associated with progression-free survival (PFS) to platinum chemotherapy using Cox proportional hazards models. The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium data sets were interrogated for frequency of significant cytobands in primary triple-negative breast cancer (pTNBC) tumors. RESULTS Among 71 evaluable patients, 17q21 and 17q22 amplifications were most strongly associated with improved PFS with platinum chemotherapy. There were no significant differences in clinicopathologic features or (neo)adjuvant chemotherapy among patients with 17q22 amplification. Patients with 17q22 amplification (n = 17) had longer median PFS with platinum (7.0 v 3.8 months; log-rank P = .015) than patients without 17q22 amplification (n = 54), an effect that remained significant in multivariable analyses (PFS hazard ratio 0.37; 95% CI, 0.16 to 0.84; P = .02). Among 39 patients who received the nonplatinum chemotherapy agent capecitabine, there was no association between 17q22 amplification and capecitabine PFS (log-rank P = .69). In The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium, 17q22 amplification occurred in more than 20% of both pTNBC and mTNBC tumors, whereas 17q21 was more frequently amplified in mTNBC relative to pTNBC (16% v 8.1%, P = .015). CONCLUSION The 17q22 amplicon, detected by ctDNA, is associated with improved PFS with platinum chemotherapy in patients with mTNBC and warrants further investigation.

scholarly journals Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1303
Author(s):  
Rizwan Ali ◽  
Hajar Al Zahrani ◽  
Tlili Barhoumi ◽  
Alshaimaa Alhallaj ◽  
Abdullah Mashhour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Line ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cell Line ◽  
Triple Negative ◽  
Cancer Cell Line

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.

scholarly journals The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Data ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lymphatic Vessels ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cancer Tissue ◽  
Expression Levels

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

scholarly journals Actionable Gene Alterations in an Asian Population With Triple-Negative Breast Cancer

2018 ◽  
pp. 1-13 ◽  
Author(s):  
Masayuki Nagahashi ◽  
YiWei Ling ◽  
Tetsu Hayashida ◽  
Yuko Kitagawa ◽  
Manabu Futamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Ethnic Diversity ◽  
Triple Negative ◽  
Asian Population ◽  
Japanese Patients ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Cancer Genes ◽  
Asian Patients

Purpose It has been suggested that the biologic characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to occur at a higher incidence in Japan than in the United States. However, most genomic studies of these tumors are from Western countries, and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96%) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35 of 53) of Japanese patients, as well as 66.7% (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration–approved drug. Conclusion Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

Prognostic and Therapeutic Values of Autophagy-related Genes in Triple-negative Breast Cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Minling Liu ◽  
Lei Li ◽  
Shan Huang ◽  
Xiaofen Pan ◽  
Huiru Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mtor Inhibitors ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Survival Curves ◽  
Prognostic Accuracy ◽  
Kaplan Meier

Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis. Therefore, it is imperative to develop new prognostic or therapeutic biomarkers for TNBC. Objective: To explore the prognostic and therapeutic values of autophagy-related genes (ARGs) in TNBC. Methods: Overall, 157 TNBC patients’ data were obtained from The Cancer Genome Atlas database, and the ARGs were acquired from the Human Autophagy Database. Differentially expressed ARGs (DEGs) between tumor and normal tissues were identified and the prognostic ARGs were developed using R software. Kaplan–Meier survival curves and receiver operating characteristic (ROC) curves were both used to evaluate the accuracy of the signature. Patents about prognostic ARGs were reviewed through Worldwide Espacenet® and Patentscope®. Results: We obtained 28 DEGs and two prognostic ARGs (EIF4EBP1 and PARP1). The Kaplan–Meier survival curves showed that the survival rate of patients with low 2-ARG signature risk score was significantly higher than that of patients with high risk score (P=0.003). ROC at 5 years indicated that the signature had good prognostic accuracy (AUC=0.929). The signature was independent of T, N, M, and TNM stage (P<0.05). Patent review suggested that many mTOR inhibitors alone or in combination with another anticancer agent have been provided for treatment of many cancers and shown promising results. No drug patents about PARP1 overexpression were disclosed. Conclusion: We developed a 2-ARG signature (EIF4EBP1 and PARP1) which was an independent prognostic biomarker for TNBC. As EIF4EBP1 was upregulated in TNBC, mTOR inhibitors which blocked the mTOR/4EBP1/eIF4E pathway may be a promising therapeutic strategy for TNBC.

scholarly journals A Synthetic Triterpenoid CDDO-Im Inhibits Tumorsphere Formation by Regulating Stem Cell Signaling Pathways in Triple-Negative Breast Cancer

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107616 ◽  
Author(s):  
Jae Young So ◽  
Janice J. Lin ◽  
Joseph Wahler ◽  
Karen T. Liby ◽  
Michael B. Sporn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Signaling Pathways

Metabolic stress induces GD2+ cancer stem cell-like phenotype in triple-negative breast cancer

2021 ◽  
Author(s):  
Appalaraju Jaggupilli ◽  
Stanley Ly ◽  
Khoa Nguyen ◽  
Vivek Anand ◽  
Bin Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metabolic Stress
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