ArticleClinical & experimental metastasis2013
Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma.
Article in Clinical & experimental metastasis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025Review
- Two Cysteines in Raf Kinase Inhibitor Protein Make Differential Contributions to Structural Dynamics In Vitro.Molecules (Basel, Switzerland) · 2025Article
- Review
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Review
- One stomach, two subtypes of carcinoma-the differences between distal and proximal gastric cancer.Gastroenterology report · 2021Review
- [MiR-4443 promotes migration and invasion of breast cancer cells by inhibiting PEBP1 expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives.Cancer medicine · 2019Review
- The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma.Cancer cell international · 2019Article
- miR-181a Upregulation Promotes Radioresistance of Nasopharyngeal Carcinoma by Targeting RKIP.OncoTargets and therapy · 2019Article
- Review
- Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives.Seminars in cancer biology · 2018Review
- Epigenetic modulation associated with carcinogenesis and prognosis of human gastric cancer.Oncology letters · 2017Article
- Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma.Oncology letters · 2017Article
- Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats.Frontiers in molecular neuroscience · 2017Article
- Article
- Clinicopathological features and prognostic implications of Raf kinase inhibitor protein downregulation in tongue squamous cell carcinoma.Oncology letters · 2015Article
- Biomarkers for gastric cancer: Progression in early diagnosis and prognosis (Review).Oncology letters · 2015Article
- Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications.World journal of gastroenterology · 2014Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Raf kinase inhibitory protein (RKIP) has been identified as a member of a novel class of molecules which implicated in cancer progression and suppress the metastatic spread of tumors. The aim of this study was to investigate the promoter methylation and expression of RKIP, determine the prognostic significance of RKIP in gastric cardia adenocarcinoma (GCA). MSP approach and immunohistochemistry methods were used respectively to examine methylation status and protein expression of RKIP in GCA tissues. The frequency of RKIP methylation in GCA tumor tissues (62.1 %) was significantly higher than that in corresponding normal tissues (4.1 %) and was associated with TNM stage, histological differentiation, depth of invasion, LN metastasis, distant metastasis or recurrence, and upper gastrointestinal cancers (UGIC) family history. Positive staining of RKIP in GCA tumor tissues (34.5 %) was significantly decreased than that in corresponding normal tissues (84.1 %) and was associated with RKIP methylation. RKIP may act as a tumor suppressor gene in GCA by regulation of the Raf-1/MEK/ERK signaling pathway. GCA patients in stage III and IV, with positive UGIC family history, and hypermethylation and down-expression of RKIP were most likely to develop metastatic disease and also showed the worse survival. RKIP methylation in GCA was an independent prognostic marker for survival using multivariate Cox regression analysis (P = 0.04). In all, aberrant hypermethylation of RKIP may be one of the mechanisms that lead to loss or down expression of the gene in GCA especially in individuals with UGIC family history. Additionally, hypermethylation and loss of RKIP expression may be used as a marker to predict clinical outcome of GCA.
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