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

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 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.

Язык: 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

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 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.

Язык: Английский

Процитировано

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

Prachi Kapse,

Shehnaz Siddique

и другие.

Cancer Biology and Medicine, Год журнала: 2023, Номер unknown, С. 1 - 20

Опубликована: Июнь 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.

Язык: Английский

Процитировано

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

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14890 - 14890

Опубликована: Окт. 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.

Язык: Английский

Процитировано

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

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 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.

Язык: Английский

Процитировано

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

и другие.

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(4), С. 3031 - 3051

Опубликована: Июль 26, 2024

Язык: Английский

Процитировано

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

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер unknown, С. 107994 - 107994

Опубликована: Ноя. 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

Язык: Английский

Процитировано

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 Avcı, Eda Açıkgöz

и другие.

Biochemical and Biophysical Research Communications, Год журнала: 2023, Номер 680, С. 194 - 210

Опубликована: Сен. 16, 2023

Язык: Английский

Процитировано

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

Wenzheng Wang

и другие.

Translational Oncology, Год журнала: 2023, Номер 35, С. 101733 - 101733

Опубликована: Июль 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

Язык: Английский

Процитировано

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

и другие.

Molecules, Год журнала: 2023, Номер 28(23), С. 7776 - 7776

Опубликована: Ноя. 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.

Язык: Английский

Процитировано

4
Oncogenic Role of SATB2 In Vitro: Regulator of Pluripotency, Self-Renewal, and Epithelial–Mesenchymal Transition in Prostate Cancer DOI Creative Commons
Wei Yu, Rashmi Srivastava,

Shivam Srivastava

и другие.

Cells, Год журнала: 2024, Номер 13(11), С. 962 - 962

Опубликована: Июнь 3, 2024

Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to attachment regions and involved in chromatin remodeling transcription regulation. In stem cells, it regulates the expression of genes required for maintaining pluripotency self-renewal epithelial–mesenchymal transition (EMT). this study, we examined oncogenic role SATB2 prostate cancer assessed whether overexpression human normal epithelial cells (PrECs) induces properties (CSCs). The results demonstrate highly expressed cell lines CSCs, but not PrECs. Overexpression PrECs cellular transformation which was evident by formation colonies soft agar spheroids suspension. also resulted induction markers (CD44 CD133), pluripotency-maintaining factors (cMYC, OCT4, SOX2, KLF4, NANOG), CADHERIN switch, EMT-related factors. Chromatin immunoprecipitation assay demonstrated can directly bind promoters BCL-2, BSP, NANOG, MYC, XIAP, HOXA2, suggesting capable regulating pluripotency/self-renewal, survival, proliferation. Since CSCs play crucial initiation, progression, metastasis, effects knockdown on stemness. inhibited spheroid formation, viability, colony motility, migration, invasion compared their scrambled control groups. upregulated E-CADHERIN N-CADHERIN, SNAIL, SLUG, ZEB1. significantly higher adenocarcinoma tissues. Overall, our data suggest acts as an factor where inducing malignant changes CSC characteristics.

Язык: Английский

Процитировано

1