Identification of interpretable clusters and associated signatures in breast cancer single cell data: a topic modeling approach DOI Creative Commons
M. Gabriele, Filippo Valle, Emmanuel Barillot

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 15, 2022

ABSTRACT Topic modeling is a popular technique in machine learning and natural language processing, where corpus of text documents classified into themes or topics using word frequency analysis. This approach has proven successful various biological data analysis applications, such as predicting cancer subtypes with high accuracy identifying genes, enhancers, stable cell types simultaneously from sparse single epigenomics data. The advantage topic model that it not only serves clustering algorithm, but can also explain results by providing probability distributions over topics. Our study proposes novel for cells detecting (gene signatures) single-cell datasets measure multiple omics simultaneously. We applied this to examine the transcriptional heterogeneity luminal triple negative breast patient-derived xenograft models acquired resistance chemotherapy targeted therapy. Through approach, we identified protein-coding genes long noncoding RNAs (lncRNAs) group thousands biologically similar clusters, accurately distinguishing drug-sensitive resistant types. In comparison standard state-of-the-art analyses, our offers optimal partitioning clusters simultaneously, producing easily interpretable outcomes. Additionally, demonstrate an integrative which combines information mRNAs lncRNAs treated disjoint layers, enhances classification.

Language: Английский

Long non-coding RNA mediated drug resistance in breast cancer DOI
Deepshikha Singh, Yehuda G. Assaraf, Rajesh N. Gacche

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 63, P. 100851 - 100851

Published: July 1, 2022

Language: Английский

Citations

99
The Clinical Utility of lncRNAs and Their Application as Molecular Biomarkers in Breast Cancer DOI Open Access
Cristian Arriaga-Canon, Laura Contreras‐Espinosa, Sergio Aguilar-Villanueva

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7426 - 7426

Published: April 18, 2023

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, treatment response. Particularly, the lncRNAs DSCAM-AS1 GATA3-AS1 serve as examples of this because high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates use clinical practice. However, lncRNA studies cancer are limited sample size restricted determination biological function, which represents an obstacle its inclusion utility. Nevertheless, due specificity among diseases, such cancer, stability body fluids, promising that could improve reliability, sensitivity, techniques used diagnosis. The development lncRNA-based diagnostics therapeutics will useful routine medical practice patient management quality life.

Language: Английский

Citations

38
CRISPR/Cas9 screen uncovers functional translation of cryptic lncRNA-encoded open reading frames in human cancer DOI Creative Commons
Caishang Zheng, Yanjun Wei, Peng Zhang

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(5)

Published: Feb. 28, 2023

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening large-scale analysis molecular/clinical data for breast cancer (BC) identified estrogen receptor α–positive (ER+) BC dependency on ORFs encoded by lncRNA genes were upregulated luminal tumors. We confirmed vivo tumor-promoting function unannotated protein, GATA3-interacting protein (GT3-INCP) LINC00992, expression which was associated poor prognosis GTE-INCP estrogen/ER regulated estrogen-dependent cell growth. Mechanistically, GT3-INCP interacted GATA3, a master transcription factor key to mammary gland development/BC proliferation, coregulated gene program involved many susceptibility/risk impacted response/cell proliferation. GT3-INCP/GATA3 bound common cis regulatory elements estrogen-regulated MYB PDZK1. Our study indicates lncRNA-encoded can be integrated component transcriptional network driving aberrant cancer, "hidden" proteome might new space therapeutic target discovery.

Language: Английский

Citations

26
Identification of Interpretable Clusters and Associated Signatures in Breast Cancer Single-Cell Data: A Topic Modeling Approach DOI Open Access
M. Gabriele, Filippo Valle, Emmanuel Barillot

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1350 - 1350

Published: March 29, 2024

Topic modeling is a popular technique in machine learning and natural language processing, where corpus of text documents classified into themes or topics using word frequency analysis. This approach has proven successful various biological data analysis applications, such as predicting cancer subtypes with high accuracy identifying genes, enhancers, stable cell types simultaneously from sparse single-cell epigenomics data. The advantage topic model that it not only serves clustering algorithm, but can also explain results by providing probability distributions over topics. Our study proposes novel for single cells detecting (gene signatures) datasets measure multiple omics simultaneously. We applied this to examine the transcriptional heterogeneity luminal triple-negative breast patient-derived xenograft models acquired resistance chemotherapy targeted therapy. Through approach, we identified protein-coding genes long non-coding RNAs (lncRNAs) group thousands biologically similar clusters, accurately distinguishing drug-sensitive -resistant types. In comparison standard state-of-the-art analyses, our offers an optimal partitioning clusters simultaneously, producing easily interpretable outcomes. Additionally, demonstrate integrative which combines information mRNAs lncRNAs treated disjoint layers, enhances classification.

Language: Английский

Citations

5
A1BG-AS1 promotes adriamycin resistance of breast cancer by recruiting IGF2BP2 to upregulate ABCB1 in an m6A-dependent manner DOI Creative Commons
Jian Wang, Jie Xu, Jie Zheng

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 25, 2023

Adriamycin (ADR) resistance is an obstacle for chemotherapy of breast cancer (BC). ATP binding cassette subfamily B member 1 (ABCB1) expression indicated to be closely related the drug cells. The current work intended explore molecular mechanisms regulate ABCB1 in BC cells with ADR resistance. We found that long noncoding RNA (lncRNA) A1BG antisense (A1BG-AS1) upregulated resistant cell lines (MCF-7/ADR, MDA-MB-231/ADR). A1BG-AS1 knockdown enhanced sensitivity by suppressing viability, proliferation potential and migration ability, facilitating apoptosis BC. Insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) known m6A reader modulate stability mRNA transcripts m6A-dependent manner, which was a shared (RBP) ABCB1. interaction IGF2BP2 or explored verified using pulldown immunoprecipitation (RIP) assays. positively regulated stabilized via recruiting manner. Moreover, rescue assays demonstrated modulating Xenograft mouse models were used whether affected vivo. findings silencing inhibited tumor alleviated In conclusion, enhances upregulate

Language: Английский

Citations

12
A Perspective on Artificial Intelligence for Molecular Pathologists DOI Creative Commons
Timothy J. O’Leary, Brian O'Leary, Dianne P. O’Leary

et al.

Journal of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Efficacy analysis of neoadjuvant chemotherapy regimens in patients with HER2/neunegative locally advanced breast cancer: A nonrandomized comparative study DOI Creative Commons
K. A. Aliev,

В В Олексенко,

Evgeniya Y. Zyablitskaya

et al.

Kuban Scientific Medical Bulletin, Journal Year: 2025, Volume and Issue: 32(2), P. 29 - 40

Published: April 29, 2025

Background. In present times, no unified standard for selecting a neoadjuvant chemotherapy regimen breast cancer exists. Although the efficacy of has been confirmed by numerous clinical studies, tumor drug resistance develops in some cases, which reduces expected effect chemotherapy. Currently, to is major cause treatment failure and one most challenging problems therapy metastatic locally advanced cancer. Objectives. To evaluate HER2/neu-negative Methods. A nonrandomized comparative study involving 187 women with verified diagnosis (human epidermal growth factor receptor) primary (T3N2, T4N0-3) was conducted. From 2020 2024, these (mean age 53.6 ± 7.8 years) underwent therapy, follow-up, examination Crimean Republican Oncological Clinical Dispensary named after V.M. Efetov, Republic Crimea. At first stage chemotherapy, all patients received combination doxorubicin cyclophosphamide intravenously once every 21 days within four courses; evaluated. next stage, taking into account immunohistochemical subtype prescribed cytostatics, studied cohort divided subgroups. Patients luminal ( n = 130) (175 mg/m 2 courses — 96 patients) dose-intensive (paclitaxel 80 week, 12 administrations 34 chemotherapies. triple-negative 57) 175 42 carboplatin AUC2 (Area under Curve) 15 The results were analyzed calculating overall objective response rate pathologic complete response. Statistical analysis performed using Microsoft Office Excel 2007 (Microsoft, USA), IBM SPSS Statistics, version 23.0 (IBM, both parametric nonparametric statistical methods. analyze differences two independent groups, Pearson’s χ test or Fisher’s exact (for comparison very small samples) used. Differences considered statistically significant at p ≤ 0.05. Results. During cancer, weekly administration taxanes anthracycline does not significantly increase detection resistant forms affected ongoing taxane days) higher 0.005). Weekly platinum-based drugs 4 courses) compared based on cytostatics 0.02). Conclusion. applied regimens are characterized high incidence post-cytotoxic complications group paclitaxel accompanied marked asthenization. this regard, priority beginning should be given antitumor drugs.

Language: Английский

Citations

0
LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis DOI
Yuxi Liu,

Shuo Yuan,

Xiaojing Liu

et al.

Journal of Molecular Medicine, Journal Year: 2022, Volume and Issue: 100(9), P. 1271 - 1286

Published: July 5, 2022

Language: Английский

Citations

8
New insights of LncRNAs fingerprints in breast cancer progression: Tumorigenesis, drug resistance, and therapeutic opportunities DOI Creative Commons
Bashdar Mahmud Hussen,

Diyar Idris Othman,

Snur Rasool Abdullah

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 287, P. 138589 - 138589

Published: Dec. 9, 2024

Breast cancer (BC) is one of the common female cancers and it characterized by considerable problems regarding its development therapy. Long non-coding RNAs (lncRNAs) have been identified as significant modulators in BC development, especially, tumorigenicity chemoresistance. We therefore endeavor to present an up-to-date understanding lncRNAs their impact on progression treatment, concerning molecular processes, treatment options, use a therapeutic opportunity. LncRNAs are novel regulators genes that cause resistance directly functioning both coding patients, but little known about mechanisms actions. Thus, additional study required deeper modes action possible roles disease. This aims investigate functions BC, with particular attention role tumorigenesis, drug mechanisms, targets. will help identify targets improve effectiveness treatment.

Language: Английский

Citations

1
Prognostic potential of m7G-associated lncRNA signature in predicting bladder cancer response to immunotherapy and chemotherapy DOI Creative Commons
Dengxiong Li,

Ruicheng Wu,

Jie Wang

et al.

ONCOLOGIE, Journal Year: 2023, Volume and Issue: 25(6), P. 729 - 742

Published: Nov. 1, 2023

Abstract Objectives The influence of N 7 -methylguanosine (m7G) on cancer prognosis and immune response has been well-reported. However, the role m7G-related long non-coding RNAs (lncRNAs) in bladder (BC) remains largely unexplored. This study wanted to explore relationship between lncRNAs BC. Methods To construct lncRNA signature, we utilized data obtained from TCGA. collected was then analyzed using R (version 4.2.1, Bell Laboratories, Boston, USA) relevant packages. Results signature consisted seven (including GATA3-AS1, LINC00930, LINC01341, MED14OS, MIR100HG, RUSC1-AS1, SNHG4). prognostic clinical relevance risk score corroborated both TCGA IMvigor210 datasets. Individuals characterized by a high-risk displayed substantial enrichment pathways associated with immunity, notably those pertaining innate response, cytokine-mediated signaling pathways, adaptive system. Additionally, group showed positive correlation many checkpoints, including CD274, CD40, CTLA4, PDCD1, PDCD1LG2, among others. Moreover, significant difference TCIA observed low-risk groups, indicating potential distinct immunotherapy rates. Furthermore, patients demonstrated increased sensitivity cisplatin, docetaxel, doxorubicin, gemcitabine, vinblastine. Conclusions demonstrates considerable promise as biomarker BC, facilitating anticipation responses chemotherapy. provides solid foundation for future investigations into

Language: Английский

Citations

3