Nature reviews. Cancer, Год журнала: 2025, Номер unknown
Опубликована: Апрель 10, 2025
Язык: Английский
Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(8), С. 610 - 627
Опубликована: Июль 4, 2024
Язык: Английский
Процитировано
29
Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)
Опубликована: Янв. 1, 2025
ABSTRACT Background Plasma protein has gained prominence in the non‐invasive predicting of lung cancer. We utilised Zeolite Zotero NaY‐based plasma proteomics to investigate its potential for multiple event predicting, including cancer diagnosis (task #1), lymph node metastasis detection #2) and tumour‒node‒metastasis (TNM) staging #3). Methods A total 4703 proteins were quantified from 241 participants based on a prospective cohort 2757 participants. An additional 46 external 735 used validation. Feature selection was performed using differential expressed analysis, area under curve (AUC) evaluation least absolute shrinkage operator (LASSO) regression. Random forest multitask model construction key proteins. importance interpreted Shapley additive explanations (SHAP) algorithm. Results For task #1, 10 panel showed an AUC .87 (.77‒.97) After integrating clinical factors, significant increase diagnostic accuracy observed with .91 (.85‒.98). #2, nine achieved .88 (.80‒.96), integration .90 (.85‒.97). #3, (.74‒.96) stage I, .92 (.84‒.97) II, (.76‒.96) III .99 (.98‒.99) IV model. Conclusions This study comprehensively profiled proteome biomarker, laying foundation high‐performance blood test events Key points Our developed innovative nanomaterial, NaY, which addressed masking effect improved depth proteome. The performance as preclinical tool validated through both internal cohort. Furthermore, we explored different patterns changes during progression method elucidate roles predictive
Язык: Английский
Процитировано
3
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Фев. 24, 2024
Abstract Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying based on elevated expression transcription factors ASCL1, NEUROD1, and POU2F3, well certain inflammatory characteristics. The role regulator YAP1 defining unique subset remains be established. Although preclinical analyses described numerous subtype-specific characteristics vulnerabilities, so far non-existing clinical subtype distinction may contributor negative trial outcomes. This comprehensive review aims provide framework for development novel personalized therapeutic approaches by compiling most discoveries achieved research. We highlight challenges faced due limited access patient material accomplished implementing state-of-the-art models methodologies.
Язык: Английский
Процитировано
18
Advanced Science, Год журнала: 2024, Номер 11(31)
Опубликована: Июнь 19, 2024
Abstract Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth and early metastasis susceptible to treatment resistance recurrence. Understanding the intra‐tumoral spatial heterogeneity in SCLC crucial for improving patient outcomes clinically relevant subtyping. In this study, whole transcriptome‐wide analysis of 25 patients at sub‐histological resolution using GeoMx Digital Spatial Profiling technology performed. This deciphered multi‐regional heterogeneity, distinct molecular profiles, biological functions, immune features, subtypes within spatially localized histological regions. Connections between different transcript‐defined phenotypes their impact on survival therapeutic response are also established. Finally, gene signature, termed ITHtyper, based prevalence levels, which enables risk stratification from bulk RNA‐seq profiles identified. The prognostic value ITHtyper rigorously validated independent multicenter cohorts. study introduces preliminary tumor‐centric, regionally targeted transcriptome resource that sheds light previously unexplored SCLC. These findings hold promise improve tumor reclassification facilitate development personalized treatments patients.
Язык: Английский
Процитировано
10
MedComm, Год журнала: 2024, Номер 5(11)
Опубликована: Ноя. 1, 2024
Abstract Circulating tumor DNA (ctDNA) methylation, an innovative liquid biopsy biomarker, has emerged as a promising tool in early cancer diagnosis, monitoring, and prognosis prediction. As noninvasive approach, overcomes the limitations of traditional tissue biopsy. Among various biomarkers, ctDNA methylation garnered significant attention due to its high specificity detection capability across diverse types. Despite immense potential, clinical application faces substantial challenges pertaining sensitivity, specificity, standardization. In this review, we begin by introducing basic biology common techniques methylation. We then explore recent advancements faced biopsies. This includes progress screening identification molecular subtypes, monitoring recurrence minimal residual disease (MRD), prediction treatment response prognosis, assessment burden, determination origin. Finally, discuss future perspectives applications. comprehensive overview underscores vital role enhancing diagnostic accuracy, personalizing treatments, effectively progression, providing valuable insights for research practice.
Язык: Английский
Процитировано
10
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1293 - 1293
Опубликована: Фев. 3, 2025
Complex RNA-seq signatures involving the transcription factors ASCL1, NEUROD1, and POU2F3 classify Small Cell Lung Cancer (SCLC) into four subtypes: SCLC-A, SCLC-N, SCLC-P, SCLC-I (triple negative or inflamed). Preliminary studies suggest that identifying these subtypes can guide targeted therapies potentially improve outcomes. This study aims to evaluate whether expression levels of three key effectively SCLC subtypes, comparable use individual antibodies in immunohistochemical (IHC) analysis formalin-fixed, paraffin-embedded (FFPE) tumor samples. We analyzed preclinical models increasing complexity, including eleven human five mouse cell lines, six patient-derived xenografts (PDXs), two circulating (CTC)-derived (CDXs) generated our laboratory. RT-qPCR conditions were established detect POU2F3. Additionally, protein-level was performed using Western blot for lines IHC FFPE samples PDX CDX tumors, following experience with patient from CANTABRICO trial (NCT04712903). found line predominantly expressed POU2F3, showed no expression, as identified by RT-qPCR, consistently matching previously assigned each line. The classification demonstrated consistency between analyses factors. Our results show single-gene FFPE-extracted RNA simplifies subtype classification. approach provides a cost-effective alternative staining expensive multi-gene sequencing panels, making subtyping more accessible both research clinical applications.
Язык: Английский
Процитировано
1
Trends in cancer, Год журнала: 2024, Номер 10(10), С. 935 - 946
Опубликована: Авг. 19, 2024
Язык: Английский
Процитировано
9
MedComm, Год журнала: 2025, Номер 6(3)
Опубликована: Фев. 21, 2025
Abstract The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, noncoding RNA changes, often precede genetic mutations are critical in progression. In this study, we explore how biopsy, combined markers, can provide cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges targeting regulators, which could disrupt cellular balance if overexploited, need maintaining key gene expressions therapeutic applications. This review highlights promise using early‐stage diagnosis, a focus on optimizing treatment strategies precision medicine.
Язык: Английский
Процитировано
1
Talanta, Год журнала: 2025, Номер 292, С. 127925 - 127925
Опубликована: Март 12, 2025
Язык: Английский
Процитировано
1
Nature Reviews Clinical Oncology, Год журнала: 2025, Номер unknown
Опубликована: Март 14, 2025
Язык: Английский
Процитировано
1