ArticleBMC cancer2017
Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 39 citations in OpenAlex.
- Time-frequency analysis of serum with proton nuclear magnetic resonance for diagnosis of pancreatic cancer.Scientific reports · 2020Trial
- A Multiomics and Bioinformatics Analysis of the Role and Mechanism ofInternational journal of genomics · 2026Article
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- Identification of hub genes in bladder cancer based on weighted gene co-expression network analysis from TCGA database.Cancer reports (Hoboken, N.J.) · 2022Article
- Discriminating Potential Genetic Markers for Complete Response and Non-Complete Response Patients to Neoadjuvant Chemotherapy with Locally Advanced Rectal Cancer.International journal of environmental research and public health · 2022Article
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- Targeting cancer epigenetics with CRISPR-dCAS9: Principles and prospects.Methods (San Diego, Calif.) · 2021Review
- Integrative analysis of DNA methylation and gene expression in papillary renal cell carcinoma.Molecular genetics and genomics : MGG · 2020Article
- CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A.BMC cancer · 2020Article
- Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDespite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease. We analyzed the expression levels of CNKSR1, a scaffold that influences MAPK/ERK pathway activity, in clinical pancreas cancer specimens and their impact on survival of patients with pancreatic cancer.
methodsImmunohistochemical staining for CNKSR1 expression was performed on 120 specimens from three independent pancreatic cancer tissue registries, phospho-ERK levels were measured in 86 samples. Expression was divided into CNKSR1 low and CNKSR1 high and correlated with clinicopathological variables including overall survival using multivariate Cox proportional hazard ratio models.
resultsCNKSR1 expression was increased in tumors compared to matched normal uninvolved resection specimens (p = 0.004). 28.3% (34/120) of patient specimens stained as CNKSR1 low compared to 71.7% (86/120) of specimens which stained as CNKSR1 high. High CNKSR1 expression was more prevalent in low grade tumors (p = 0.04). In multivariate analysis, low CNKSR1 expression status was independently correlated with decreased overall survival (HR = 2.146; 95% CI 1.34 to 3.43). When stratifying primary, non-metastatic tumor biopsies by CNKSR1 expression, resection was associated with improved survival in patients with high CNKSR1 expression (p < 0.0001) but not low CNKSR1 expression (p = 0.3666). Pancreatic tumors with nuclear in addition to cytoplasmic CNKSR1 staining (32/107) showed increased nuclear phospho-ERK expression compared to tumor with cytoplasmic CNKSR1 staining only (p = 0.017).
conclusionCNKSR1 expression is increased in pancreatic tissue specimens and was found to be an independent prognostic marker of overall survival. CNKSR1 may help to identify patient subgroups with unfavorable tumor biology in order to improve risk stratification and treatment selection. Cellular distribution of CNKSR1 was correlated with nuclear pERK expression.
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