Transfer RNA-Derived RNAs As Novel Predictive Biomarkers of Chemotherapy Resistance in Breast Cancer

2019 ◽  
Author(s):  
Han Ge ◽  
Yangyang Cui ◽  
Yue Huang ◽  
Mingjie Zheng ◽  
Xiaowei Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chemotherapy Resistance ◽  
Predictive Biomarkers ◽  
Transfer Rna

MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells.

2017 ◽  
Vol 12 (1) ◽  
pp. 221-229
Author(s):  
Abeer M. Ashmawy ◽  
Mona A. Sheta ◽  
Faten Zahran ◽  
Abdel Hady A. Abdel Wahab
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Predictive Biomarkers

Identification of biomarkers and functional modules from genomic data in stage-wise breast cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Athira K ◽  
Vrinda C ◽  
Sunil Kumar P V ◽  
Gopakumar G
Keyword(s):  
Breast Cancer ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Predictive Biomarkers ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Functional Modules ◽  
Incidence And Mortality ◽  
Multiple Stages

Background: Breast cancer is the most common cancer in women across the world, with high incidence and mortality rates. Being a heterogeneous disease, gene expression profiling based analysis plays a significant role in understanding breast cancer. Since expression patterns of patients belonging to the same stage of breast cancer vary considerably, an integrated stage-wise analysis involving multiple samples is expected to give more comprehensive results and understanding of breast cancer. Objective: The objective of this study is to detect functionally significant modules from gene co-expression network of cancerous tissues and to extract prognostic genes related to multiple stages of breast cancer. Methods: To achieve this, a multiplex framework is modelled to map the multiple stages of breast cancer, which is followed by a modularity optimization method to identify functional modules from it. These functional modules are found to enrich many Gene Ontology terms significantly that are associated with cancer. Result and Discussion: predictive biomarkers are identified based on differential expression analysis of multiple stages of breast cancer. Conclusion: Our analysis identified 13 stage-I specific genes, 12 stage-II specific genes, and 42 stage-III specific genes that are significantly regulated and could be promising targets of breast cancer therapy. That apart, we could identify 29, 18 and 26 lncRNAs specific to stage I, stage II and stage III respectively.

scholarly journals Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Jia-Teng Zhong ◽  
Jian Yu ◽  
Hai-Jun Wang ◽  
Yu Shi ◽  
Tie-Suo Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Viability ◽  
Human Breast Cancer ◽  
Chemotherapy Resistance ◽  
Mtor Signaling Pathway ◽  
Human Breast ◽  
Diphenyltetrazolium Bromide ◽  
Mcf 7

Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway–related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V–fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V–fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

BIOM-32. ENDOPLASMIC RETICULUM PROTEIN SSR3 DETERMINES AND PREDICTS RESPONSE TO PACLITAXEL IN BREAST CANCER AND GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi17-vi18
Author(s):  
Crismita Dmello ◽  
Aarón Sonabend ◽  
Víctor Arrieta ◽  
Daniel Zhang ◽  
Deepak Kanojia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Glioma Cells ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Precision Oncology ◽  
Patient Response ◽  
Knock Out ◽  
Genome Wide ◽  
A Genome

Abstract Paclitaxel (PTX) is one the most potent and commonly used chemotherapies for breast and pancreatic cancer. Given the potency of this drug for glioblastomas (GBM) several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood-brain barrier for this disease. In spite of the efficacy of PTX, individual tumors exhibit variable susceptibility to this drug, with response rate in the range of 30%-60%. To identify predictive biomarkers for response to PTX, we performed a genome-wide CRISPR knock-out screen using human glioma cells. The most enriched genes in the CRISPR screen underwent further selection based on their correlation with survival in the breast cancer patient cohorts treated with PTX and not in patients treated with other chemotherapies, a finding that was validated on a second independent patient cohort. This led to the discovery of endoplasmic reticulum (ER) protein SSR3 as a putative predictive biomarker for PTX. SSR3 protein levels showed positive correlation with response to PTX in breast cancer cells, glioma cells, in multiple intracranial glioma xenografts and in GBM patient derived explant cultures. Knockout of SSR3 turned the cells resistant to PTX while its overexpression sensitized the cells to PTX. In gliomas, SSR3-mediated susceptibility to PTX relates to modulation of phosphorylation of ER stress sensor IRE1α. Thus, by using genome-wide screen combined with patient response data, we discovered a biomarker that demonstrates causal and correlative relationship with response to PTX in breast cancer and GBM. Prospective validation of this biomarker is warranted for its broad implementation for precision oncology.

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