Identification of Noninvasive Biomarkers for Gallbladder Carcinoma

BackgroundCarcinoma of the gallbladder (GBC) is an aggressive malignancy of the hepatobiliary system with a poor prognosis due to late presentation and a lack of effective diagnostic tools.Conventional imaging often fails to accurately detect the disease in its early stages.Both abdominal USG and contrast-enhanced computed tomography (CECT) have lower sensitivities for early-stage GBC.This highlights the need for reliable noninvasive biomarkers that may facilitate early diagnosis and improve clinical outcomes.These novel molecular markers may be used alone or in combination with serum tumor markers to enhance their diagnostic utility.This study was performed to identify novel, noninvasive biomarkers for the diagnosis of GBC and determine their accuracy in differentiating carcinoma from other benign pathologies of the gallbladder. Materials and methodsThis prospective observational case-control study was conducted over a period of one year, from April 2025 to March 2026, in the Department of General Surgery, Motilal Nehru Medical College, Prayagraj.A total of 60 patients were included, comprising 30 histologically confirmed GBC cases and 30 controls with benign gallbladder disease.Detailed clinical evaluations, laboratory investigations, and imaging studies were performed.Blood samples were collected prior to intervention, and biomarkers, including carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA-125, were analyzed using ELISA, while microRNA (miRNA)-21 and miRNA-155 were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques.Statistical analysis was performed, and diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis. ResultsPatients with GBC showed significantly higher levels of the tumor markers CA 19-9, CEA, and CA-125 compared to controls (p < 0.001).The molecular biomarkers miRNA-21 and miRNA-155 were also markedly elevated in carcinoma cases and strongly correlated with tumor stage and histological grade.The combination of biomarkers (CA 19-9 and miRNA-21) showed superior diagnostic accuracy (91.7%), with higher sensitivity (93.3%) and specificity (90%) on ROC analysis (area under the curve (AUC) of 0.956).Clinical and radiological findings were consistent with advanced disease in most cases. ConclusionNoninvasive biomarkers, particularly when used in combination, demonstrate high diagnostic accuracy for the early detection of GBC.Integration of biomarker analysis with clinical and radiological evaluation can further improve diagnostic utility and facilitate better clinical management.These findings support the potential role of biomarker-based screening strategies in high-risk populations.