Ann Surg Treat Res.  2023 Feb;104(2):90-100. 10.4174/astr.2023.104.2.90.

Expression levels of RUNX3 and FGFR2 in peripheral blood of severe acute pancreatitis and their clinical significance

• Liang Y
• Ding H

• KMID: 2539223
• DOI: http://doi.org/10.4174/astr.2023.104.2.90

Abstract

Purpose
Severe acute pancreatitis (SAP) is a life-threatening inflammatory syndrome of the pancreas. This study aimed to analyze the clinical significance of runt-associated transcription factor 3 (RUNX3) and fibroblast growth factor receptor 2 (FGFR2) expression alterations in SAP.
Methods
This study included 18 SAP patients in Wuzhong People’s Hospital from November 2019 to December 2021 and 18 healthy controls. RUNX3 and FGFR2 expression levels were determined by RT-quantitative PCR. Correlations between RUNX3/FGFR2 and sex, age, etiology, CRP, procalcitonin, AST, LDH, BUN, Acute Physiology and Chronic Health Evaluation II (APACHE II), Ranson score, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, sequential organ failure assessment (SOFA), and modified computed tomography severity index (MCTSI) score were analyzed. Diagnostic values of RUNX3 and FGFR2 in SAP were analyzed using the receiver-operating characteristic curve. The binding of RUNX3 to FGFR2 was analyzed by chromatin immunoprecipitation.
Results
RUNX3 and FGFR2 were downregulated in peripheral blood of SAP patients. RUNX3 and FGFR2 were negatively correlated with CRP, procalcitonin, AST, LDH, BUN, APACHE II score, Ranson score, BISAP score, SOFA score, and MCTSI score. Sensitivity and specificity of RUNX3 level of <0.9650 for SAP diagnosis were 88.89% and 72.22%, respectively. Sensitivity and specificity of FGFR2 level of <0.8950 for SAP diagnosis were 66.67% and 83.33%, respectively. RUNX3 was enriched in the FGFR2 promoter and was positively correlated with FGFR2.
Conclusion
RUNX3 and FGFR2 were downregulated in peripheral blood of SAP patients and served as candidate biomarkers for SAP diagnosis. RUNX3 bound to the FGFR2 promoter to promote FGFR2 transcription.

Keyword

Clinical relevance; Fibroblast growth factor receptor 2; Pancreatitis; Runt-associated transcription factor 3; Serum

Figure

• 

  Fig. 1 RUNX3 is downregulated in peripheral blood of SAP patients and has high diagnostic values. (A) RUNX3 levels in peripheral blood of SAP patients and the control group were determined by RT-quantitative PCR. (B) ROC curve based on the diagnostic value of RUNX3 in SAP. Data in panel A were analyzed using the independent-sample t-test. SAP, severe acute pancreatitis; ROC, receiver-operating characteristic; AUC, the area under the curve; SE, standard error.

• 

  Fig. 2 RUNX3 expression is correlated with clinicopathological characteristics of SAP patients. (A–K) Correlations between RUNX3 expression in peripheral blood and CRP, PCT, LDH, AST, BUN, APACHE II score, Ranson score, BISAP score, SOFA score, and MCTSI score in 18 SAP patients were analyzed using Pearson correlation analysis. SAP, severe acute pancreatitis; PCT, procalcitonin; APACHE II, Acute Physiology and Chronic Health Evaluation II; BISAP, Bedside Index for Severity in Acute Pancreatitis; SOFA, sequential organ failure assessment; MCTSI, modified computed tomography severity index.

• 

  Fig. 3 FGFR2 is downregulated in peripheral blood of SAP patients and has high diagnostic values. (A) FGFR2 levels in peripheral blood of SAP patients and the control group were determined by RT-quantitative PCR. (B) ROC curve based on the diagnostic value of FGFR2 in SAP. Data in panel A were analyzed using the independent-sample t-test. SAP, severe acute pancreatitis; ROC, receiver-operating characteristic; AUC, the area under the curve; SE, standard error. *P < 0.05.

• 

  Fig. 4 FGFR2 expression is correlated with clinicopathological characteristics of SAP patients. (A–K) Correlations between FGFR2 expression in peripheral blood and CRP, PCT, LDH, AST, BUN, APACHE II score, Ranson score, BISAP score, SOFA score, and MCTSI score in 18 SAP patients were analyzed using Pearson correlation analysis. SAP, severe acute pancreatitis; PCT, procalcitonin; APACHE II, Acute Physiology and Chronic Health Evaluation II; BISAP, Bedside Index for Severity in Acute Pancreatitis; SOFA, sequential organ failure assessment; MCTSI, modified computed tomography severity index.

• 

  Fig. 5 RUNX3 expression is positively correlated with FGFR2 expression in peripheral blood of SAP patients. (A) The binding of RUNX3 to the FGFR2 promoter was predicted on the JASPAR database (http://jaspar.genereg.net/). (B) The enrichment of RUNX3 on the FGFR2 promoter was analyzed by the ChIP assay. (C) Correlation between RUNX3 expression and FGFR2 expression in peripheral blood of 18 SAP patients was analyzed by Pearson correlation analysis. Cell experiments were performed 3 times independently. Data in panel B were expressed as mean ± standard deviation and analyzed using the t-test. IgG, immunoglobulin G; SAP, severe acute pancreatitis; ChIP, chromatin immunoprecipitation. *P < 0.05.

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