Acute pancreatitis is one of the most common gastrointestinal disorders requiring hospital admission worldwide, and its incidence continues to climb year after year. For roughly 80 percent of patients the disease runs a mild course and resolves without complications, but the remaining 20 percent develop serious local and systemic complications that sharply increase morbidity and mortality. The trouble for clinicians is that the disease is notoriously heterogeneous: it begins with abnormal enzyme activation inside pancreatic acinar cells, triggering local inflammation that can spiral into a full systemic inflammatory response. Key mechanisms driving this process include the release of inflammatory cytokines, disruption of cellular calcium homeostasis, mitochondrial dysfunction and oxidative stress. Because the clinical trajectory is so variable, predicting prognosis in the early hours of the disease remains one of the field’s most stubborn challenges, and no single laboratory marker has yet proven capable of reliably reflecting disease severity on its own.
A new prospective clinical study published in the Journal of Cellular and Molecular Medicine offers a fresh molecular angle on this problem by examining a family of proteins that has rarely been studied in human pancreatitis: the ATP-binding cassette, or ABC, transporters. These transporters form a large protein superfamily that functions as ATP-dependent pumps, moving a wide range of endogenous and exogenous compounds across cell membranes. In doing so, they help maintain cellular barrier functions, preserve cellular homeostasis and regulate cellular stress responses. Importantly, their expression is known to be modulated by inflammatory signalling and various forms of cellular stress, which makes them plausible players in a disease defined by exactly those processes. Yet, until now, the expression levels of ABC transporter genes in acute pancreatitis and their relationship to clinical and radiological severity had not been sufficiently clarified.
The research team, working at the University of Health Sciences Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital in Türkiye, focused on two specific members of the transporter family. The first, ABCG2, located on chromosome 4q22, mediates the efflux of diverse substrates out of the cell through an ATP-dependent mechanism and has been linked to protection against oxidative stress in experimental systems. The second, ABCC2, also known as MRP2, is expressed not only in the liver but also in human pancreatic tissue, particularly on the apical membrane of ductal cells, where it contributes to the export of toxic metabolites and inflammatory mediators. Given these functional profiles, both genes were considered candidates for involvement in the inflammatory and cellular stress pathways that underpin acute pancreatitis.
The study enrolled 80 patients hospitalized with acute pancreatitis between December 2023 and January 2025, alongside 96 healthy controls matched for age and sex who had no acute or chronic inflammatory disease, infection, rheumatologic condition, or chronic liver or kidney disease. Diagnosis followed standard criteria, requiring at least two of three features: typical abdominal pain, serum amylase or lipase at least three times the upper limit of normal, or compatible imaging findings. Clinical severity was assessed with the Ranson score at admission and at 48 hours, while radiological severity was classified using computed tomography in strict accordance with the revised Atlanta classification, distinguishing mild disease from moderately severe disease with transient organ failure or local complications and severe disease with persistent organ failure beyond 48 hours.
The molecular workflow was straightforward but rigorous. Peripheral venous blood samples were collected from all participants, and after routine biochemical analyses were completed, remaining blood was centrifuged, separated and stored at minus 80 degrees Celsius. Total RNA was extracted from whole blood using a TRIzol-based method, with concentration and purity verified spectrophotometrically. Complementary DNA was synthesized and the expression levels of ABCG2 and ABCC2 were quantified by quantitative real-time polymerase chain reaction, with β-actin serving as the internal control. All reactions were run in triplicate and relative gene expression was calculated using the 2^(−ΔΔCt) method, a standard approach that normalizes target gene signals to a stable reference gene.
The demographic picture of the cohort reflected the typical profile of acute pancreatitis. The mean age of patients was 49.74 years, statistically indistinguishable from the control group’s 47.96 years, and 60 percent of patients were male. Gallstones were by far the most common cause of the disease, accounting for 52.5 percent of cases, followed by alcohol use at 15 percent, hyperlipidemia at 5 percent, medication-related causes at 3.75 percent and other etiologies at 23.75 percent. Clinically, the median total Ranson score was 3, and 57.5 percent of patients were classified as having severe disease by that score. Radiologically, however, 83.7 percent of patients showed mild disease on computed tomography, with only 16.3 percent classified as moderate or severe. Pleural effusion occurred in 11.3 percent of patients, 7.5 percent needed supplemental oxygen, 5 percent required intensive care, and the median hospital stay was six days.
The central molecular findings were striking. ABCG2 expression was significantly lower in patients with acute pancreatitis than in healthy controls, with a median expression of 0.29 in the patient group versus 0.58 in controls, a difference that reached statistical significance at p = 0.025. ABCC2, by contrast, showed no significant difference between patients and controls, with a median of 1.54 in patients versus 0.89 in controls and a p-value of 0.172. When the researchers stratified patients by Ranson score, neither gene distinguished mild from severe clinical disease; ABCG2 showed a non-significant trend toward higher expression in severe cases at p = 0.098, while ABCC2 showed no relationship at all. The picture changed, however, when severity was assessed radiologically: ABCG2 expression was significantly higher in the moderate and severe group defined by computed tomography, with a median of 1.05 versus 0.21 in mild cases, a difference that was statistically significant at p = 0.038.
Receiver operating characteristic analysis added further nuance. The area under the curve for ABCG2 as a discriminator of acute pancreatitis was 0.598, with a 95 percent confidence interval of 0.515 to 0.682, a statistically significant but modest discriminatory performance. The authors interpret this carefully: the fact that ABCG2 expression is lower in patients overall suggests it is unlikely to serve as a stand-alone diagnostic marker. Instead, they argue, the gene may function as a dynamic indicator of the underlying inflammatory and cellular stress biology. They propose a plausible mechanism: the intense cytokine response and cellular stress during the acute inflammatory phase may initially suppress ABCG2 expression, while a compensatory upregulation emerges in more severe cases as oxidative burden and cellular injury accumulate. This interpretation is consistent with prior experimental work showing that ABCG2 can reduce oxidative stress and apoptosis, and with evidence that reactive oxygen species, disrupted calcium homeostasis, mitochondrial dysfunction and ATP depletion drive acinar cell necrosis in pancreatitis.
The findings also align with earlier animal data. In a rat model of chronic pancreatitis, researchers including members of the same team had previously observed changes in ABCG2 and ABCC2 expression in the setting of chronic inflammation, with melatonin administration influencing oxidative and endoplasmic reticulum stress parameters tied to these genes. The present human study, however, reveals a different pattern: suppression of ABCG2 overall but elevation in radiologically severe cases. The authors attribute these differences to the distinct biology of acute versus chronic inflammation, interspecies variation and the use of peripheral blood rather than pancreatic tissue. Notably, the stronger association of ABCG2 with radiological rather than clinical severity may reflect the fact that computed tomography more directly demonstrates morphological injury, including necrosis and local complications, whereas clinical scores may under-capture severity in the early phase. The study’s limitations include its single-centre design, modest sample size and reliance on blood samples, but its strengths are considerable: it is the first study to evaluate ABCG2 and ABCC2 expression in human acute pancreatitis, and by linking molecular data to both clinical scores and imaging classifications it provides original evidence that ABCG2 may be a dynamically regulated candidate biomarker of inflammatory and cellular stress in this unpredictable disease.
Subject of Research: ABCG2 and ABCC2 transporter gene expression and its relationship to disease severity in acute pancreatitis
Article Title: ABCG2 and ABCC2 Expression Levels and Their Relationship With Disease Severity in Acute Pancreatitis
Article References: Baş, S., Güzel Tanoğlu, E., Tanoğlu, A., Karahan, H. T., Gökçe, M. S., Yeniçeri, M., Şenoymak, M. C., & Arslan, K. (2026). ABCG2 and ABCC2 Expression Levels and Their Relationship With Disease Severity in Acute Pancreatitis. Journal of Cellular and Molecular Medicine, 30(18), Article e71368. https://doi.org/10.1111/jcmm.71368
Image Credits: AI Generated
DOI: 10.1111/jcmm.71368
Keywords: acute pancreatitis, ABCG2, ABCC2, ABC transporters, gene expression, Ranson score, revised Atlanta classification, computed tomography, oxidative stress, biomarkers, qRT-PCR, inflammation
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Juliet Wilcox. (September 21, 2026). ABC Transporter Gene ABCG2 Emerges as a Dynamic Marker of Acute Pancreatitis Severity. Scienmag. https://scienmag.com/abc-transporter-gene-abcg2-emerges-as-a-dynamic-marker-of-acute-pancreatitis-severity/
Juliet Wilcox. “ABC Transporter Gene ABCG2 Emerges as a Dynamic Marker of Acute Pancreatitis Severity.” Scienmag, 21 September 2026, https://scienmag.com/abc-transporter-gene-abcg2-emerges-as-a-dynamic-marker-of-acute-pancreatitis-severity/. Accessed 21 September 2026.
Juliet Wilcox. “ABC Transporter Gene ABCG2 Emerges as a Dynamic Marker of Acute Pancreatitis Severity.” Scienmag. September 21, 2026. https://scienmag.com/abc-transporter-gene-abcg2-emerges-as-a-dynamic-marker-of-acute-pancreatitis-severity/
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Tags: ABC transportersABCC2ABCG2acute pancreatitisBiomarkerscomputed tomographygene expressioninflammationOxidative stressqRT-PCRRanson scorerevised Atlanta classification
