ArticlePloS one2014
REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.World journal of gastroenterology · 2023Pooled it
- Emerging insights into exosomal protein functions in colorectal cancer.Discover oncology · 2026Review
- REG/Reg family proteins: mediating gut microbiota homeostasis and implications in digestive diseases.Gut microbes · 2025Review
- Controversial Roles of Regenerating Family Proteins in Tissue Repair and Tumor Development.Biomedicines · 2024Review
- Upregulation of REG IV gene in human intestinal epithelial cells by lipopolysaccharide via downregulation of microRNA-24.Journal of cellular and molecular medicine · 2022Article
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- Mechanism of Lysoforte in Improving Jejuna Morphology and Health in Broiler Chickens.Frontiers in veterinary science · 2022Article
- REG4 promotes the proliferation and anti-apoptosis of cancer.Frontiers in cell and developmental biology · 2022Review
- Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2021Article
- Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular CaProceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Article
- Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.Frontiers in immunology · 2021Article
- The Clinical Significance and Mechanisms of REG4 in Human Cancers.Frontiers in oncology · 2020Review
- Article
- Reg Gene Expression in Periosteum after Fracture and Its In Vitro Induction Triggered by IL-6.International journal of molecular sciences · 2017Article
- Colon cancer subtypes: concordance, effect on survival and selection of the most representative preclinical models.Scientific reports · 2016Article
- Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- REG4 promotes peritoneal metastasis of gastric cancer through GPR37.Oncotarget · 2016Article
- REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.PloS one · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionColorectal cancer (CRC) is one of the world's three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulated expression occurs in inflammatory bowel diseases also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed. Our aim was to investigate tumor REG4 expression in CRC patients and its coexpression with other intestinal markers.
methodsTumor expression of REG4 was evaluated by immunohistochemistry in 840 consecutive surgically treated CRC patients at Helsinki University Central Hospital. Expression of MUC1, MUC2, MUC5AC, synapthophysin, and chromogranin was evaluated in a subgroup of 220 consecutively operated CRC patients. REG4 expression with clinicopathological parameters, other intestinal markers, and the impact of REG4 expression on survival were assessed.
resultsREG4 expression associated with favorable clinicopathological parameters and with higher overall survival from non-mucinous CRC (p = 0.019). For such patients under 65, its expression was an independent marker of lower risk of death within 5 years that cancer; univariable hazard ratio (HR) = 0.57; 95% confidence interval (CI) (0.34-0.94); multivariable HR = 0.55; 95% CI (0.33-0.92). In non-mucinous CRC, REG4 associated with positive MUC2, MUC4, and MUC5AC expression.
conclusionWe show, to our knowledge for the first time, that REG4 IHC expression to be an independent marker of favorable prognosis in non-mucinous CRC. Our results contradict those from studies based on quantification of REG4 mRNA levels, a discrepancy warranting further studies.
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