Unveiling novel double-negative prostate cancer subtypes through single-cell RNA sequencing analysis DOI Creative Commons
Siyuan Cheng,

Lin Li,

Yunshin Yeh

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Aug. 2, 2024

Abstract Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising publicly available cohorts generated by our research team, established H uman P rostate S ingle cell A tlas (HuPSA) M ouse (MoPSA) datasets. Through comprehensive analysis, identified two novel double-negative PCa populations: KRT7 cells characterized elevated expression progenitor-like marked SOX2 FOXA2 expression, distinct NEPCa, displaying stem/progenitor features. Furthermore, HuPSA-based deconvolution re-classified human specimens, validating presence these subtypes. We then developed a user-friendly web application, “HuPSA–MoPSA” ( https://pcatools.shinyapps.io/HuPSA-MoPSA/ ), for visualizing gene across all newly Our study provides tools uncovers that can inform clinical diagnosis treatment strategies.

Language: Английский

Novel hormone therapies for advanced prostate cancer: understanding and countering drug resistance DOI Creative Commons
Zhipeng Wang, Jie Wang,

Dengxiong Li

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101232 - 101232

Published: Feb. 1, 2025

Language: Английский

Citations

2
Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells DOI Creative Commons
Yi Zhou, Yue Sun, Qiongyan Zhang

et al.

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 4, 2025

At all stages of gastric cancer (GC), cisplatin is the first-line chemotherapeutic agent, but its efficacy remains limited, with a response rate less than 20%, largely because resistance to drug. It aims determine whether macrophage-derived exosomes are involved in mechanism resistance, order identify potential methods for reversing and improving patient outcomes. Macrophages induced by IL-13 IL-4 were characterized using flow cytometry, then co-cultured GC cells cisplatin. Cell viability apoptosis subsequently evaluated through CCK-8 assays cytometry. Exosome miR-194, derived from M2 macrophages, was assess cell survival. Furthermore, mouse model established, miR-194 injected observe tumor growth. Results indicate that macrophages enhance mainly as demonstrated assays. Cellular uptake experiments can transfer exert functional effects. Western blotting PCR analysis further confirmed inhibits enhances downregulating PTEN. Macrophage-derived promotes inhibiting PTEN downregulation. These findings provide new insights theoretical backing clinical treatment strategies GC.

Language: Английский

Citations

1
Emerging clinical applications of single-cell RNA sequencing in oncology DOI
Emily Boxer,

Nisan Feigin,

Roi Tschernichovsky

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

Citations

1
Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer DOI Open Access
Tao Ding,

Lina He,

Guo-Wen Lin

et al.

Chinese Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 37(1), P. 90 - 114

Published: Jan. 1, 2025

Prostate cancer (PCa) is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment (TME) and high heterogeneity, which challenges clinically stratified management reinforces need for novel strategies to fight against castration-resistant PCa (CRPC). We performed single-cell RNA sequencing (scRNA-seq) on 10 untreated primary tissues integrated public scRNA-seq resources from three normal prostate tissues, two six CRPC tumors portray comprehensive molecular interaction atlas of PCa. further bulk transcriptomes establish classification system. profiles revealed substantial inter- intra-tumoral heterogeneity across different cell subpopulations in tumors. In malignant epithelial reservoir, cells evolved along decoupled paths treatment-naive tumors, distinct transcriptional reprogramming processes were activated, highlighting anti-androgen therapy-induced lineage plasticity. Based specifically expressed markers subpopulations, we conducted unsupervised clustering analysis The Cancer Genome Atlas adenocarcinoma (TCGA-PRAD) cohort identified molecularly subtypes. C1 subtype, enrichment CRPC-enriched cells, had risk rapid development resistance might require active surveillance additional promising intervention treatments, such as integrin A3 (ITGA3) + B1 (ITGB1) inhibition. C2 subtype resembled immune-modulated that was most likely benefit anti-LAG3 immunotherapy. C3 favorable prognosis. Our study provides high-resolution landscape intricate architecture TME, our trichotomic taxonomy could help facilitate precision oncology.

Language: Английский

Citations

1
CellPie: a scalable spatial transcriptomics factor discovery method via joint non-negative matrix factorization DOI Creative Commons
Sokratia Georgaka, William Geraint Morgans, Qian Zhao

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(6)

Published: March 20, 2025

Abstract Spatially resolved transcriptomics has enabled the study of expression genes within tissues while retaining their spatial identity. Most (ST) technologies generate a matched histopathological image as part standard pipeline, providing morphological information that can complement data. Here, we present CellPie, fast, unsupervised factor discovery method based on joint non-negative matrix factorization RNA transcripts and histological features. CellPie employs accelerated hierarchical least squares to significantly reduce computational time, enabling efficient application high-dimensional ST datasets. We assessed three different human cancer types with resolutions, including highly Visium HD dataset, demonstrating both good performance high efficiency compared existing methods.

Language: Английский

Citations

1
The future of tumor organoids in precision therapy DOI Creative Commons
Seok-Young Kim,

Marc van de Wetering,

Hans Clevers

et al.

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Tumoroids are cultures of patient-derived tumor cells, which grown in 3D the presence an extracellular matrix extract and specific growth factors. can be generated from adult as well pediatric cancers, including epithelial sarcomas, brain cancers. retain multi-omic characteristics their corresponding recapitulate interpatient intratumor heterogeneity. Retrospective prospective studies have demonstrated that tumoroids predict patient responses to anticancer therapies, making them a promising tool for precision oncology. However, several challenges remain before fully integrated into clinical decision-making, success rates tumoroid establishment turnaround times. This review discusses current advances, challenges, future directions tumoroid-based models cancer research therapy.

Language: Английский

Citations

1
Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies DOI Creative Commons
Josephine Yates, Agnieszka Kraft, Valentina Boeva

et al.

Genome biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 9, 2025

Abstract Background Single-cell transcriptomics has transformed our understanding of cellular diversity, yet noise from technical artifacts and low-quality cells can obscure key biological signals. A common practice is filtering out with a high percentage mitochondrial RNA counts (pctMT), typically indicative cell death. However, commonly used thresholds, primarily derived studies on healthy tissues, may be overly stringent for malignant cells, which often naturally exhibit higher baseline gene expression. Results We examine nine public single-cell RNA-seq datasets various cancers, including 441,445 134 patients, spatial data, assessing the viability pctMT. Our analysis reveals that significantly pctMT than nonmalignant without notable increase in dissociation-induced stress scores. Malignant show metabolic dysregulation, increased xenobiotic metabolism, relevant to therapeutic response. Analysis cancer lines further links drug resistance. also observe associations between transcriptional heterogeneity, as well patient clinical features. Conclusions This study provides insights into functional characteristics elevated pctMT, challenging current quality control practices tumor analyses offering potential improvements data interpretation future studies.

Language: Английский

Citations

1
Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine DOI Open Access
Giulia Spagnol, Francesca Sensi, Orazio De Tommasi

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(7), P. 2059 - 2059

Published: March 30, 2023

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to high prevalence advanced stages diagnosis and recurrence. Furthermore, heterogeneity OC tumors contributes rapid development resistance conventional chemotherapy. In recent years, in order overcome these problems, targeted therapies have been introduced various types tumors, including cancer. However, lack predictive biomarkers showing different clinical benefits limits effectiveness therapies. This requires preclinical models that can replicate histological molecular characteristics subtypes. this scenario, organoids become an important model for personalized medicine. fact, patient-derived (PDO) recapture tumor with possibility performing drug screening. best reproduce patient's characteristics, it is necessary develop a specific extracellular matrix (ECM) introduce microenvironment (TME), which both represent actual object study improve screening, particularly when used therapy immunotherapy guide therapeutic decisions. review, we summarize current state art screening PDOs, ECM, TME, drugs setting OC, as well discussing implications future perspectives research organoids.

Language: Английский

Citations

20
Single-cell omics traces the heterogeneity of prostate cancer cells and the tumor microenvironment DOI Creative Commons
Xudong Yu, Ruijia Liu, Wenfeng Gao

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: May 9, 2023

Abstract Prostate cancer is one of the more heterogeneous tumour types. In recent years, with rapid development single-cell sequencing and spatial transcriptome technologies, researchers have gained a intuitive comprehensive understanding heterogeneity prostate cancer. Tumour-associated epithelial cells; cancer-associated fibroblasts; complexity immune microenvironment, distribution cells other cancer-promoting molecules play crucial role in growth, invasion, metastasis Single-cell multi-omics biotechnology, especially sequencing, reveals expression level single higher resolution finely dissects molecular characteristics different cells. We reviewed literature on cells, focusing RNA sequencing. And we analysed differences cell discussed impact novel omics such as rich exploration strategies, joint analysis modes, deep learning models, future research. this review, constructed catalogue studies This article aimed to provide thorough diagnosis treatment summarised proposed several key issues directions applying transcriptomics understand Finally, trends

Language: Английский

Citations

20
Advances in landscape and related therapeutic targets of the prostate tumor microenvironment DOI Creative Commons

Duocai Li,

Weidong Xu,

Yifan Chang

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2023, Volume and Issue: 55(6), P. 956 - 973

Published: May 10, 2023

The distinct tumor microenvironment (TME) of prostate cancer (PCa), which promotes proliferation and progression, consists various stromal cells, immune a dense extracellular matrix (ECM). understanding the TME extends to tertiary lymphoid structures (TLSs) metastasis niches provide more concise comprehension metastasis. These constituents collectively structure hallmarks pro-tumor TME, including immunosuppressive, acidic, hypoxic niches, neuronal innervation, metabolic rewiring. In combination with knowledge advancement emerging therapeutic technologies, several strategies have been developed, some them tested in clinical trials. This review elaborates on PCa components, summarizes TME-targeted therapies, provides insights into carcinogenesis, strategies.

Language: Английский

Citations

19