Circulating REG4 as an Independent Predictor of Cachexia in Gastric Cancer: Transcriptomic Evidence and Clinical Validation.

Background: Cancer cachexia (CAC) is a prevalent and debilitating complication in gastric cancer. However, specific tumor‐derived biomarkers for the screening and diagnosis of CAC remain largely unidentified. This study was designed to screen cachectic factors secreted by tumors and to investigate t...

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Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 2026; pp. 1 - 12
Autores principales: Zhang, Zhige, Xi, Qiulei, Sui, Xiangyu, Tan, Shanjun, Lu, Yiding, Yan, Mingyue, Zhuang, Qiulin, Wu, Guohao, Liu, Hongda
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 5/21/2026
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 5/21/2026
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      pub: Wiley-Blackwell
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        10.1155/jcpt/3216731
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        atl: Circulating REG4 as an Independent Predictor of Cachexia in Gastric Cancer: Transcriptomic Evidence and Clinical Validation.
      aug:
        au:
          Zhang, Zhige
          Xi, Qiulei
          Sui, Xiangyu
          Tan, Shanjun
          Lu, Yiding
          Yan, Mingyue
          Zhuang, Qiulin
          Wu, Guohao
          Liu, Hongda
        affil: Department of General Surgery Gastrointestinal Surgery/Shanghai Clinical Nutrition Research Center, , Zhongshan Hospital, , Fudan University, , Shanghai, 200032, , China, fudan.edu.cn
      sug:
        subj:
          Cachexia Risk Factors
          Stomach Neoplasms
          Transcriptomes
          Proteins
          Tumor Markers, Biological
          Predictive Value of Tests
          Risk Assessment
          Human
          Funding Source
          Female
          Male
          Middle Age
          Aged
          Comparative Studies
          Path Analysis
          Correlational Studies
          Descriptive Statistics
          Data Analysis Software
          T-Tests
          Mann-Whitney U Test
          Chi Square Test
          Fisher's Exact Test
          Pearson's Correlation Coefficient
          Spearman's Rank Correlation Coefficient
          Univariate Statistics
          Multivariate Analysis
          Logistic Regression
          Odds Ratio
          Confidence Intervals
          ROC Curve
          Immunohistochemistry
          Enzyme-Linked Immunosorbent Assay
          Tomography, X-Ray Computed
          Tumor Necrosis Factor
          Sequence Analysis
          Gene Expression
          Body Composition
          Nutritional Status
          Middle Aged: 45-64 years
          Aged: 65+ years
          Female
          Male
      ab: Background: Cancer cachexia (CAC) is a prevalent and debilitating complication in gastric cancer. However, specific tumor‐derived biomarkers for the screening and diagnosis of CAC remain largely unidentified. This study was designed to screen cachectic factors secreted by tumors and to investigate the value of regenerating islet‐derived family member 4 (REG4) in CAC. Methods: We enrolled 91 gastric cancer patients, stratified into a CAC group (n = 34) and a noncachectic (NC) group (n = 57). To identify cachectic factors differentially expressed by tumor tissues, bulk RNA sequencing was performed. REG4 expression was validated in tumor tissues and plasma using immunohistochemistry and enzyme‐linked immunosorbent assay, respectively. CT imaging was utilized to evaluate body composition parameters, specifically the skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI). The relationships among plasma REG4 levels, nutritional status, and body composition were analyzed. Logistic regression analysis was employed to identify risk factors for CAC, and receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of REG4. Results: RNA sequencing revealed significantly elevated REG4 gene expression in the gastric cancer tumors from the CAC group compared with the NC group. Plasma REG4 levels in the CAC group were significantly higher (p < 0.001). Correlation analysis demonstrated that elevated plasma REG4 was significantly associated with lower SMI (r = −0.24, p = 0.02), SATI (r = −0.26, p = 0.01), BMI (r = −0.26, p = 0.01), and prealbumin (r = −0.22, p = 0.04), as well as increased 6‐month weight loss (r = 0.36, p < 0.001). Multivariate logistic regression and ROC curve analysis identified high REG4 levels as an independent risk factor (OR = 7.54, 95% CI: 2.63–21.65) and a potential predictor for CAC (AUC = 0.728, 95% CI: 0.626–0.831, p < 0.001). Conclusion: In patients with gastric cancer, tumor‐derived REG4 is released into the circulation, resulting in elevated plasma levels that correlate with poor nutritional status and compromised body composition. Circulating REG4 holds promise as a novel predictor for the clinical diagnosis of CAC.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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