Unmasking Neuroendocrine Prostate Cancer with a Machine Learning-Driven 7-Gene Stemness Signature that Predicts Progression DOI Creative Commons
Agustina Sabater, Pablo Sanchis, Rocio Seniuk

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

ABSTRACT Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate (NEPC). This study developed and validated stemness-associated gene signature using advanced machine learning techniques, including Random Forest Lasso regression, applied large-scale transcriptomic datasets. The resulting 7-gene ( KMT5C, MEN1, TYMS, IRF5, DNMT3B, CDC25B DPP4 ) was across independent cohorts patient-derived xenograft (PDX) models. demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, overall survival. Importantly, the not only identified specific NEPC subtypes, such as large-cell carcinoma, which is associated with very poor outcomes, but also predicted prognosis PCa cases that exhibit this molecular signature, even when they were histopathologically classified NEPC. dual classifier capability makes robust tool personalized medicine, providing valuable resource predicting disease guiding treatment strategies in management.

Language: Английский

Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy DOI Creative Commons
Yaxuan Wang, Li Ma, Jiaxin He

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 29, 2024

Background Cancer stem cells (CSCs) are a subset of within tumors that possess the unique ability to self-renew and give rise diverse tumor cells. These crucial in driving metastasis, recurrence, resistance treatment. The objective this study was pinpoint essential regulatory genes associated with CSCs prostate adenocarcinoma (PRAD) assess their potential significance diagnosis, prognosis, immunotherapy patients PRAD. Method utilized single-cell analysis techniques identify cell-related evaluate relation patient prognosis PRAD through cluster analysis. By utilizing datasets employing various machine learning methods for clustering, diagnostic models were developed validated. random forest algorithm pinpointed HSPE1 as most prognostic gene among genes. Furthermore, delved into association between immune infiltration, employed molecular docking investigate relationship its compounds. Immunofluorescence staining 60 tissue samples confirmed expression correlation Result This identified 15 analysis, highlighting importance diagnosing, prognosticating, potentially treating patients. specifically linked response immunotherapy, experimental data supporting upregulation poorer prognosis. Conclusion Overall, our findings underscore significant role unveil novel target related cell.

Language: Английский

Citations

24
Therapeutic implications of cancer stem cells in prostate cancer DOI Creative Commons
Pinaki P. Banerjee,

Prachi Kapse,

Shehnaz Siddique

et al.

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 20

Published: June 5, 2023

Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated populations originate small subset cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem (PCSCs), play crucial roles progression, drug resistance, relapse. review discusses origin, hierarchy, plasticity PCSCs; methods for isolation enrichment various metabolic signaling pathways involved PCSC induction maintenance, as well therapeutic targeting.

Language: Английский

Citations

14
Prostate Cancer Stem Cells: Biology and Treatment Implications DOI Open Access
Ioannis M. Koukourakis, Kalliopi Platoni, Vassilis Kouloulias

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14890 - 14890

Published: Oct. 4, 2023

Stem cells differentiate into mature organ/tissue-specific at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in context certain diseases. It is postulated that proliferation and carcinomas are sustained by presence vital cellular compartment resembling stem residing tissues: 'stem-like cancer cells' (CSCs). Mutations prostate lead to formation cancer. Prostate CSCs (PCSCs) have been identified partially characterized. These express surface markers include CD44, CD133, integrin α2β1, pluripotency factors like OCT4, NANOG, SOX2. Several signaling pathways also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK HH. Moreover, PCSCs appear induce resistance radiotherapy chemotherapy, while has linked aggressive behavior higher relapse rates. The development treatment policies target tumors appealing as through cell killing, trigger tumor repopulation via activated cells. Thus, blocking this reactive mobilization may facilitate positive outcome cytotoxic treatment.

Language: Английский

Citations

11
Estrogen-related receptor alpha (ERRα) controls the stemness and cellular energetics of prostate cancer cells via its direct regulation of citrate metabolism and zinc transportation DOI Creative Commons
Taiyang Ma, Wenjuan Xie, Zhenyu Xu

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 5, 2025

Compared to most tumors that are more glycolytic, primary prostate cancer is less glycolytic but dependent on TCA cycle coupled with OXPHOS for its energy demand. This unique metabolic energetic feature attributed activation of mitochondrial m-aconitase in caused by decreased cellular Zn level. Evidence suggests a small subpopulation cells within tumors, designated as stem (PCSCs), play significant roles advanced progression. However, their energetics status still poorly understood. Nuclear receptor ERRα (ESRRA) key regulator metabolism. Previous studies characterize exhibits an upregulation and can perform multiple oncogenic functions. Here, we demonstrate novel role the control stemness metabolism PCSCs via mechanism combined transrepression transporter ZIP1 reducing intracellular uptake transactivation ACO2 (m-aconitase) completion cycle. Results also showed restoration accumulation treatment ionophore Clioquinol could significantly suppress both vitro growth vivo tumorigenicity, implicating enhanced be potential therapeutic approach targeting cancer.

Language: Английский

Citations

0
Targeting Hepatic Cancer Stem Cells (CSCs) and Related Drug Resistance by Small Interfering RNA (siRNA) DOI

Saade Abdalkareem Jasim,

Omar Dheyauldeen Salahdin,

H. Malathi

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(4), P. 3031 - 3051

Published: July 26, 2024

Language: Английский

Citations

2
The molecular features of lung cancer stem cells (LCSCs) in dedifferentiation process-driven epigenetic alterations DOI Creative Commons
Valentina Masciale, Federico Banchelli, Giulia Grisendi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107994 - 107994

Published: Nov. 1, 2024

Cancer stem cells (CSCs) may be dedifferentiated somatic following oncogenic processes, representing a subpopulation of able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which main cause resistance therapies. It has been shown that the "less differentiated process" have an impact on plasticity, particularly when non-CSCs dedifferentiate become CSC-like. Bidirectional interconversion between CSCs reported in other solid tumors, where inflammatory stroma promotes cell reprogramming by enhancing Wnt signaling through NF-κB activation association intracellular signaling, induce cells' pluripotency, transformation can considered another important aspect acquisition "new" development programs features. During reprogramming, mutations represent initial step towards dedifferentiation, tumour switch from partially or terminally stage less is mainly manifested re-entry into cycle, cell-like phenotype expression markers. This phenomenon typically shows up as change form, function, pattern gene protein expression, more specifically, CSCs. review would highlight epigenetic alterations, major pathways driver cancer cells, tumors lung cancer, could involved, acting key elements differentiation/dedifferentiation process. molecular mechanisms need tailored

Language: Английский

Citations

2
Doxorubicin-induced senescence promotes resistance to cell death by modulating genes associated with apoptotic and necrotic pathways in prostate cancer DU145 CD133+/CD44+ cells DOI
Cansu Tatar, Çığır Biray Avci, Eda Açıkgöz

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 680, P. 194 - 210

Published: Sept. 16, 2023

Language: Английский

Citations

6
Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment DOI Creative Commons
Lin Li, Jianyu Liu,

Wenzheng Wang

et al.

Translational Oncology, Journal Year: 2023, Volume and Issue: 35, P. 101733 - 101733

Published: July 6, 2023

Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node (LNM) is key prognostic marker associated with distant organ reduced patient survival, but mechanisms underlying its promotion breast stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME facilitate LNM. Utilizing single-cell RNA sequencing, we profiled in primary corresponding metastatic lymph samples from patients at our institution. To verify derived data, cultured performed validation assays employing flow cytometry CyTOF. analysis revealed distinct differences cellular infiltration patterns between LNM samples. Importantly, RAC2 PTTG1 double-positive CSCs, which exhibit highest stem-like attributes, were markedly enriched nodes. These hypothesized foster via activation of specific metastasis-related transcription factors signaling pathways. Additionally, data suggest that might modulate adaptive innate evolution, thereby further contributing metastasis. In summary, this illuminates critical role modifying The enrichment highly nodes offers novel therapeutic targeting opportunities deepens understanding

Language: Английский

Citations

5
Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells’ Proliferation, Stemness, Invasion, and Apoptosis via the MAPK Pathway DOI Creative Commons

Jinyue Duan,

Yi Wang, Yuanyuan Chen

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(23), P. 7776 - 7776

Published: Nov. 25, 2023

This study explored the role of lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells’ (CCSCs) proliferation and invasion. LY6D was knocked down using siRNA, down-regulation verified Western blotting. After knockdown, CCSCs’ proliferation, stemness, invasion were suppressed, whereas apoptosis increased. Gene Ontology (GO) enrichment analysis revealed that differentially expressed genes (DEGs) between siLY6D negative control groups significantly enriched cell–substrate adherens junction, focal adhesion, junction terms. Meanwhile, Kyoto Encyclopedia Genes Genomes (KEGG) DEGs MAPK pathway. In addition, blotting results showed pBRAF pERK1/2, cascade kinases pathway, down-regulated after knockdown. nude mice xenograft experiments treatment decreased tumor sizes weights improved tumor-bearing survival rates compared with group. conclusion, these findings indicate LY6D, which is highly CCSCs, a key factor involved growth development might be potential marker therapeutic target for cancer.

Language: Английский

Citations

4
Prostate cancer stem cells and their targeted therapies DOI Creative Commons
Huilan Su, Liqun Huang, Jianjun Zhou

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 8, 2024

Prostate cancer (PCa) is the most common malignancy among men worldwide. Through androgen receptor signaling inhibitor (ARSI) treatment, patients eventually succumb to castration-resistant prostate (CRPC). For this, stem cells (PCSCs), as a minor population of tumor that can promote relapse, ARSI resistance, and disease progression, are gaining attention. Therefore, specific therapy targeting PCSCs has momentum. This study reviewed identification characterization PCSC-based putative biomarkers summarized their mechanisms action. We further discussed clinical trials novel therapeutic interventions focused on PCSC-related pathways, PCSC microenvironment, cutting-edge miRNA therapy, immunotherapy approaches from mechanistic standpoint. review provides updated insights into plasticity, identifying new optimized treatments for with advanced PCa.

Language: Английский

Citations

1