A Multimodal Deep Neural Network for Human Breast Cancer Prognosis Prediction by Integrating Multi-Dimensional Data

IEEE/ACM Transactions on Computational Biology and Bioinformatics, Journal Year: 2018, Volume and Issue: 16(3), P. 841 - 850

Published: Feb. 15, 2018

Breast cancer is a highly aggressive type of with very low median survival. Accurate prognosis prediction breast can spare significant number patients from receiving unnecessary adjuvant systemic treatment and its related expensive medical costs. Previous work relies mostly on selected gene expression data to create predictive model. The emergence deep learning methods multi-dimensional offers opportunities for more comprehensive analysis the molecular characteristics therefore improve diagnosis, prevention. In this study, we propose Multimodal Deep Neural Network by integrating Multi-dimensional Data (MDNNMD) cancer. novelty method lies in design our method's architecture fusion data. performance evaluation results show that proposed achieves better than single-dimensional other existing approaches. source code implemented TensorFlow 1.0 library be downloaded Github: https://github.com/USTC-HIlab/MDNNMD.

Language: Английский

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Liquid biopsy in breast cancer: A comprehensive review

Clinical Genetics, Journal Year: 2019, Volume and Issue: 95(6), P. 643 - 660

Published: Jan. 24, 2019

Breast cancer is the most common among women worldwide. Due to its complexity in nature, effective breast treatment can encounter many challenges. Traditional methods of detection such as tissue biopsy are not comprehensive enough capture entire genomic landscape tumors. However, with introduction novel techniques, application liquid has been enhanced, enabling improvement various aspects management including early diagnosis and screening, prediction prognosis, relapse, serial sampling efficient longitudinal monitoring disease progress response treatment. Various components tumor cells released into blood circulation be analyzed sampling, some which include circulating (CTCs), DNA (ctDNA), cell‐free RNA, tumor‐educated platelets exosomes. These utilized for different purposes. As an example, ctDNA sequenced genetic profiling tumors enhance individualized screening. CTC plasma count analysis or after curative resection surgery could facilitate minimal residual disease, aiding initiation adjuvant therapy prevent recurrence. Furthermore, assessed determine stage prognosis cancer. In this review, we discuss advantages limitations used will expand on that require further focus future research.

Language: Английский

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PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

International Journal of Cancer, Journal Year: 2017, Volume and Issue: 141(7), P. 1402 - 1412

Published: June 14, 2017

The expression of PD‐L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial‐to‐mesenchymal transition (EMT), all which are common features a highly tumorigenic subpopulation cells termed stem (CSCs). Hitherto, the intrinsic role dynamics CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics several vitro vivo assays. Expression profiling large dataset (530 patients) showed statistically significant correlation ( p < 0.0001, r = 0.36) between stemness score cancer. Specific knockdown using ShRNA revealed its critical embryonic cell transcriptional factors: OCT‐4A, Nanog factor, BMI1. Conversely, these factors could be induced upon ectopic that normally negative. Global proteomic analysis hinted for central AKT biology expressing cells. Indeed, positive effect on OCT‐4A was dependent activation. Most importantly, downregulation compromised self‐renewal capability as shown by tumorsphere formation assay extreme limiting dilution assay, respectively. This study demonstrates novel sustaining identifies molecular pathways would targeted anti‐PD‐L1 therapy.

Language: Английский

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Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: May 28, 2024

Triple-negative breast cancer (TNBC) poses significant challenges in oncology due to its aggressive nature, limited treatment options, and poorer prognosis compared other subtypes. This comprehensive review examines the therapeutic diagnostic landscape of TNBC, highlighting current strategies, emerging therapies, future directions. Targeted including PARP inhibitors, immune checkpoint EGFR hold promise for personalized approaches. Challenges identifying novel targets, exploring combination developing predictive biomarkers must be addressed optimize targeted therapy TNBC. Immunotherapy represents a transformative approach TNBC treatment, yet biomarker identification, overcoming resistance persist. Precision medicine approaches offer opportunities tailored based on tumor biology, but integration multi-omics data clinical implementation present requiring innovative solutions. Despite these challenges, ongoing research efforts collaborative initiatives hope improving outcomes advancing strategies By addressing complexities biology effective approaches, treatments can realized, ultimately enhancing lives patients. Continued research, trials, interdisciplinary collaborations are essential realizing this vision making meaningful progress management.

Language: Английский

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Challenges in the management of advanced, ER-positive, HER2-negative breast cancer

Nature Reviews Clinical Oncology, Journal Year: 2015, Volume and Issue: 12(9), P. 541 - 552

Published: May 26, 2015

Language: Английский

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Canine mammary tumors as a model for human disease (Review)

Oncology Letters, Journal Year: 2018, Volume and Issue: unknown

Published: April 2, 2018

Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has focused on dog as a model cancer. Dogs develop mammary tumors other types spontaneously with an intact immune system, which exhibit number clinical molecular similarities to HBC. In addition spontaneous tumor presentation, between canine (CMT) include age at onset, hormonal etiology course diseases. Furthermore, factors that affect disease outcome, including size, stage lymph node invasion, are similar in HBC CMT. Similarly, characteristics steroid receptor, epidermal growth factor, proliferation marker, metalloproteinase cyclooxygenase expression, mutation p53 suppressor gene CMT, mimic ductal carcinomas situ glands particularly their pathological, visual characteristics. These CMT indicate could be excellent study disease. discussed detail present review, compared vitro vivo animal available.

Language: Английский

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In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: Nov. 16, 2016

Abstract Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable signatures of specific phenotype or reliable disease biomarkers. In the present study, we introduce in silico Pathway Activation Network Decomposition Analysis (iPANDA) as scalable robust method biomarker identification using gene expression The iPANDA combines precalculated coexpression data with importance factors based on degree differential topology decomposition obtaining scores. Using Microarray Quality Control (MAQC) sets pretreatment Taxol-based neoadjuvant breast cancer therapy multiple sources, demonstrate that provides significant noise reduction identifies highly signatures. We successfully apply stratifying patients according their sensitivity therapy.

Language: Английский

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Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Cancers, Journal Year: 2020, Volume and Issue: 12(10), P. 2727 - 2727

Published: Sept. 23, 2020

One of the promising directions in personalized medicine is use three-dimensional (3D) tumor models such as spheroids and organoids. Spheroids organoids are cultures cells that can be obtained from patient tissue and, using high-throughput methods, provide a suitable therapy for patient. These 3D most types tumors, which provides opportunities creation biobanks with appropriate materials used to screen drugs facilitate development therapeutic agents. It should noted would expand understanding biology its microenvironment, help develop new vitro platforms drug testing create strategies. In this review, we discuss spheroid organoid models, their advantages disadvantages, evaluate medicine.

Language: Английский

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Breast cancer‐specific survival by clinical subtype after 7 years follow‐up of young and elderly women in a nationwide cohort

International Journal of Cancer, Journal Year: 2018, Volume and Issue: 144(6), P. 1251 - 1261

Published: Oct. 27, 2018

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. identified 21,384 women diagnosed with at ages 20-89 between 2005 2015 in Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone (PR) human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), B-like HER2-negative (ER+PR-HER2-), HER2-positive (ER+PR+/-HER2+), (ER-PR-HER2+) triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) cancer-specific 7-year survival by age subtype, while adjusting year, grade, TNM stage treatment. Young more often had TNBC tumors, elderly (70-89) tumors. Compared 50-59, young doubled mortality rate (HR = 2.26, 95% CI 1.81-2.82), two five times higher (70-79: HR 2.25, 1.87-2.71; 80-89: 5.19, 4.21-6.41). After adjustments, association non-significant among remained high elderly. associated increased old all subtypes. were strong independent factors. The always did worse, also after adjustment subtype. Tumor-associated (subtype, grade stage) largely explained young. Future studies should why a women.

Language: Английский

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Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer

PLoS Medicine, Journal Year: 2015, Volume and Issue: 12(9), P. e1001871 - e1001871

Published: Sept. 1, 2015

Background Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity caused by metastases that remain incurable to date. TGF-β1 has been identified as key driving force behind metastatic breast cancer, with promising therapeutic implications. Methods and Findings Employing immunohistochemistry (IHC) analysis, we report, our knowledge for first time, asporin overexpressed in stroma of most human cancers not expressed normal tissue. In vitro, secreted fibroblasts upon exposure conditioned medium from some but all cells. While hormone receptor (HR) positive cells cause strong expression, triple-negative (TNBC) suppress it. Further, findings show soluble IL-1β, TNBC cells, responsible inhibiting cancer-associated fibroblasts. Using recombinant protein, well synthetic peptide fragment, demonstrate ability inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial mesenchymal transition, stemness two vivo murine models TNBC, observed tumors expressing exhibit significantly reduced growth (2-fold; p = 0.01) properties (3-fold; 0.045). A retrospective IHC study performed on carcinoma (n 180) demonstrates expression lowest HER2+ tumors, while HR+ have higher (4-fold; 0.001). Assessment patient outcome 60; 10-y follow-up) shows low protein levels primary lesion delineate patients bad regardless tumor HR status (area under curve 0.87; 95% CI 0.78–0.96; 0.0001). Survival based gene 375; 25-y follow-up), confirmed are associated likelihood survival (hazard ratio 0.58; 0.37–0.91; 0.017). Although these data highlight potential serve prognostic marker, confirmation clinical value would require prospective much larger cohort. Conclusions Our stroma-derived inhibitor suppressor cancer. High less aggressive stratifying according outcome. Future pre-clinical studies should consider options increasing strategy targeted therapy.

Language: Английский

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