A novel approach to identify subtype-specific network biomarkers of breast cancer survivability

Jubair, Sheikh; Alkhateeb, Abedalrhman; Tabl, Ashraf Abou; Rueda, Luis; Ngom, Alioune

doi:10.1007/s13721-020-00249-4

Cited by 29 publications

(16 citation statements)

References 37 publications

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“…There is extensive diversity among breast cancer patients, and each sub-type of breast cancer has unique characteristics. The identification of sub-type-specific network biomarkers can be useful in predicting the survivability of breast cancer patients [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

et al. 2021

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We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)-positive MCF-7 breast cancer cells identified 5-((2H-1,2,3-triazol-1-yl)(3,4,5-trimethoxyphenyl)methyl)-2-methoxyphenol 24 as a potent antiproliferative compound with an IC50 value of 52 nM in MCF-7 breast cancer cells (ER+/PR+) and 74 nM in triple-negative MDA-MB-231 breast cancer cells. The compounds demonstrated significant G2/M phase cell cycle arrest and induction of apoptosis in the MCF-7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF-10A breast cells. The immunofluorescence staining of MCF-7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds 19e, 21l, and 24 in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds 19e and 21l were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule-disrupting agents for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

et al. 2021

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“…A recent study reported that a novel network-based approach can identify the biomarkers of breast cancer survivability. 10 …”

Section: Introductionmentioning

confidence: 99%

“…A recent study reported that a novel network-based approach can identify the biomarkers of breast cancer survivability. 10 We identified genes involved in metastatic TNBC through a comprehensive analysis of the Cancer Genome Atlas (TCGA) gene expression data. Weighted gene co-expression network analysis (WGCNA) is a systems biology method to describe the patterns in correlations of genes among samples.…”

Section: Introductionmentioning

confidence: 99%

Identification of Metastasis-Associated Genes in Triple-Negative Breast Cancer Using Weighted Gene Co-expression Network Analysis

Xie

Chen

et al. 2020

Evol Bioinform Online

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Triple-negative breast cancer (TNBC) is the most aggressive and fatal sub-type of breast cancer. This study aimed to identify metastasis-associated genes that could serve as biomarkers for TNBC diagnosis and prognosis. RNA-seq data and clinical information on TNBC from the Cancer Genome Atlas were used to conduct analyses. Expression data were used to establish co-expression modules using average linkage hierarchical clustering. We used weighted gene co-expression network analysis to explore the associations between gene sets and clinical features and to identify metastasis-associated candidate biomarkers. The K-M plotter website was used to explore the association between the expression of candidate biomarkers and patient survival. In addition, receiver operating characteristic curve analysis was used to illustrate the diagnostic performance of candidate genes. The pale turquoise module was significantly associated with the occurrence of metastasis. In this module, 64 genes were identified, and its functional enrichment analysis revealed that they were mainly associated with transcriptional misregulation in cancer, microRNAs in cancer, and negative regulation of angiogenesis. Further, 4 genes, IGSF10, RUNX1T1, XIST, and TSHZ2, which were negatively associated with relapse-free survival and have seldom been reported before in TNBC, were selected. In addition, the mRNA expression levels of the 4 candidate genes were significantly lower in TNBC tumor tissues compared with healthy tissues. Based on the K-M plotter, these 4 genes were correlated with poor prognosis of TNBC. The area under the curve of IGSF10, RUNX1T1, TSHZ2, and XIST was 0.918, 0.957, 0.977, and 0.749. These findings provide new insight into TNBC metastasis. IGSF10, RUNX1T1, TSHZ2, and XIST could be used as candidate biomarkers for the diagnosis and prognosis of TNBC metastasis.

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“…Prognosis and treatment depend strongly on the cancer stage at diagnosis and the molecular subtype with the worst prognosis in stage IV and triple-negative BC [10]. Further classification methods based on genetic profiles are being developed to allow an even more accurate prognosis for recurrence and survival to further personalize treatment approaches [11,12]. In addition to classification and therapeutic improvements, changes in BC prognosis over time as well as variations across countries are affected by the implementation of mammography screening programs.…”

Section: Introductionmentioning

confidence: 99%

Divergent Patterns and Trends in Breast Cancer Incidence, Mortality and Survival Among Older Women in Germany and the United States

Jansen

Holleczek

Kraywinkel

et al. 2020

Cancers

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Background: Breast cancer treatment has changed tremendously over the last decades. In addition, the use of mammography screening for early detection has increased strongly. To evaluate the impact of these developments, long-term trends in incidence, mortality, stage distribution and survival were investigated for Germany and the United States (US). Methods: Using population-based cancer registry data, long-term incidence and mortality trends (1975–2015), shifts in stage distributions (1998–2015), and trends in five-year relative survival (1979–2015) were estimated. Additionally, trends in five-year relative survival after standardization for stage were explored (2004–2015). Results: Age-standardized breast cancer incidence rates were much higher in the US than in Germany in all periods, whereas age-standardized mortality began to lower in the US from the 1990s on. The largest and increasing differences were observed for patients aged 70+ years with a 19% lower incidence but 45% higher mortality in Germany in 2015. For this age group, large differences in stage distributions were observed, with 29% (Germany) compared to 15% (US) stage III and IV patients. Age-standardized five-year relative survival increased strongly between 1979–1983 and 2013–2015 in Germany (+17% units) and the US (+19% units) but was 9% units lower in German patients aged 70+ years in 2013–2015. This difference was entirely explained by differences in stage distributions. Conclusions: Overall, our results are in line with a later uptake and less extensive utilization of mammography screening in Germany. Further studies and efforts are highly needed to further explore and overcome the increased breast cancer mortality among elderly women in Germany.

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A novel approach to identify subtype-specific network biomarkers of breast cancer survivability

Cited by 29 publications

References 37 publications

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

Identification of Metastasis-Associated Genes in Triple-Negative Breast Cancer Using Weighted Gene Co-expression Network Analysis

Divergent Patterns and Trends in Breast Cancer Incidence, Mortality and Survival Among Older Women in Germany and the United States

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