ArticlePancreas
Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index.
Article in Pancreas. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Multiomic analyses delineate human neuroendocrine tumor cell states in relation to normal enteroendocrine cell ontogeny.The Journal of clinical investigation · 2026Article
- Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).Oncology letters · 2026Review
- GSK3i combinatorial treatments affect CDK4/6 and compensatory pathways in 3D preclinical models of pancreatic neuroendocrine tumors.Biology open · 2026Article
- CCND1 Stability Regulated by USP7 Deubiquitination Controls Glioma Radioresistance via Ferroptosis.Analytical cellular pathology (Amsterdam) · 2026Article
- Review
- HER2-positive neuroendocrine breast carcinoma: a case study uncoversPathologica · 2025Article
- Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.Journal of surgical oncology · 2024Article
- CDHu40: a novel marker gene set of neuroendocrine prostate cancer.Briefings in bioinformatics · 2024Article
- Nucleocytoplasmic β-catenin expression contributes to neuroendocrine differentiation in muscle invasive bladder cancer.Cancer science · 2024Article
- Article
- The Role of Rab GTPases in the development of genetic and malignant diseases.Molecular and cellular biochemistry · 2024Review
- Platelet-derived circRNAs signature in patients with gastroenteropancreatic neuroendocrine tumors.Journal of translational medicine · 2023Article
- Cyclin-dependent Kinases 4/6 Inhibitors in Neuroendocrine Neoplasms: from Bench to Bedside.Current oncology reports · 2022Review
- Downregulated miR-150-5p in the Tissue of Nasopharyngeal Carcinoma.Genetics research · 2022Article
- Long non-coding RNA LINC01296 promotes progression of oral squamous cell carcinoma through activating the MAPK/ERK signaling pathway via the miR-485-5p/PAK4 axis.Archives of medical science : AMS · 2022Article
- Review
- Effect of metastatic site on survival in patients with neuroendocrine neoplasms (NENs). An analysis of SEER data from 2010 to 2014.BMC endocrine disorders · 2020Article
- Molecular prognostic factors in small-intestinal neuroendocrine tumours.Endocrine connections · 2019Article
- MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1.Cancer management and research · 2019Article
- Clinical significance of microRNA-449a in hepatocellular carcinoma with microarray data mining together with initial bioinformatics analysis.Experimental and therapeutic medicine · 2018Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesDysregulation of the cell cycle has been observed and implicated as an etiologic factor in a range of human malignancies, but remains relatively unstudied in neuroendocrine tumors (NETs). We evaluated expression of key proteins involved in cell cycle regulation in a large cohort of NETs.
methodsWe evaluated immunohistochemical expression of CDKN1B, CDKN1A, CDKN2A, CDK2, CDK4, CDK6, cyclin D1, cyclin E1, and phosphorylated retinoblastoma protein (phospho-RB1) in a cohort of 267 patients with NETs. We then explored associations between cell cycle protein expression, mutational status, histologic features, and overall survival.
resultsWe found that high expression of CDK4, CDK6, CCND1, and phospho-RB1 was associated with higher proliferative index, as defined by MKI67. We additionally observed a trend toward shorter overall survival associated with low expression of CDKN1B. This association seemed strongest in SINETs (multivariate hazards ratio, 2.04; 95% confidence interval, 1.06-3.93; P = 0.03). We found no clear association between CDKN1B mutation and protein expression.
conclusionsOur results suggest that dysregulation and activation of the CDK4/CDK6-CCND1-phospho-RB1 axis is associated with higher proliferative index in NETs. Investigation of the therapeutic potential of CDK4/CDK6 inhibitors in higher grade NETs is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.