Background: The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.
Methods: The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.
Results: Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06-2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44-9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41-4.40; P = 0.0019).
Conclusions: Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1245/s10434-014-3659-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
FoxC1 activates Notch3 signaling to promote the inflammatory phenotype of keloid fibroblasts and aggravates keloid.
Exp Cell Res
January 2025
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui, 230032, China. Electronic address:
Keloids are disfiguring proliferative scars, and their pathological mechanisms are still unclear. We have previously established that FoxC1 plays a significant role in rheumatoid arthritis and osteoarthritis, but its molecular mechanisms in pathological scar formation remain elusive. In this study, we analyzed keloid tissue characteristics using HE staining and immunohistochemistry, revealing abnormal expression of FoxC1 and Notch3 in keloids.
View Article and Find Full Text PDFA NOTCH3 pathogenic variant influences osteogenesis and can be targeted by antisense oligonucleotides in induced pluripotent stem cells.
PLoS One
January 2025
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.
View Article and Find Full Text PDFA pilot study of transcriptomic preimplantation genetic testing (PGT-T): towards a new step in embryo selection?
Hum Reprod
December 2024
IVIRMA Global Research Alliance, IVI Foundation, Health Research Institute La Fe, Valencia, Spain.
Study Question: Is it possible to predict an euploid chromosomal constitution and identify a transcriptomic profile compatible with extended embryonic development from RNA sequencing (RNA-Seq) data?
Summary Answer: It has been possible to obtain a karyotype comparable to preimplantation genetic testing for aneuploidy (PGT-A), in addition to a transcriptomic signature of embryos which might be suggestive of improved implantation capacity.
What Is Known Already: Conventional assessment of embryo competence, based on morphology and morphokinetic, lacks knowledge of molecular aspects and faces controversy in predicting ploidy status. Understanding the embryonic transcriptome is crucial, as gene expression influences development and implantation.
Baihu Jia Renshen Decoction may improve skeletal muscle and adipose tissue functions of type I diabetic rats by affecting pancreatic β-cell function.
Genes Genomics
December 2024
Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, No. 1, Futian District, Shenzhen, 518033, Guangdong, China.
Background: Baihu Jia Renshen Decoction (BJRD) is used for diabetes mellitus (DM) management in clinics.
Objective: To elucidate the potential mechanism of BJRD in treating type 1 DM (T1DM).
Methods: T1DM models were established via intraperitoneal injection of streptozotocin (STZ).
Genome-wide DNA methylation and gene expression in human placentas derived from assisted reproductive technology.
Commun Med (Lond)
December 2024
Environmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
Background: Assisted reproductive technology (ART) has been associated with increased risks for growth disturbance, disrupted imprinting as well as cardiovascular and metabolic disorders. However, the molecular mechanisms and whether they are a result of the ART procedures or the underlying subfertility are unknown.
Methods: We performed genome-wide DNA methylation (EPIC Illumina microarrays) and gene expression (mRNA sequencing) analyses for a total of 80 ART and 77 control placentas.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!