Serum calreticulin as a promising biomarker for cancer screening

Background: Calreticulin (CALR) is an endoplasmic reticulum chaperone protein that can translocate to the plasma membrane during cellular stress. Despite its known roles in cancer, CALR levels in the blood have not been extensively studied in cancer patients. We hypothesized that serum CALR is elevated in cancer patients and may serve as a noninvasive biomarker for early detection. Methods: Serum samples were collected from patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), breast cancer (BC), colorectal cancer (CRC), and healthy donors. CALR concentration was quantified using a RayBiotech Human CALR Sandwich ELISA. Statistical analyses were performed using Mann-Whitney U tests for group comparisons and ROC analysis for evaluating diagnostic performance on GraphPad Prism. Results: 80 PDAC patients, 25 BC patients, 25 CRC patients, and 60 healthy donors were included in the study. Median (IQR) CALR level increased from 36.22 pg/mL (5.09-264.6) in healthy individuals to 363.1 pg/mL (226.5-729.7) in PDAC patients, 182.5 pg/mL (108.1-344.0) in CRC patients, and 584.9 pg/mL (381.2-823.4) in BC patients. Pairwise testing confirmed significantly higher CLAALR levels in PDAC vs. healthy (p <0.0001), BC vs. healthy (p < 0.0001), and CRC vs. healthy (p = 0.0021).ROC analysis demonstrated strong diagnostic potential of serum CALR for distinguishing PDAC from healthy individuals (AUC = 0.799). The optimal cutoff, determined using Youden's Index, was 147 pg/mL with a sensitivity of 89% and specificity of 71.7%. Differentiating healthy donors from BC was also significant (AUC = 0.844) with sensitivity of 88% and specificity of 73.33% at the optimal cutoff value of 308.7 pg/mL. CRC was also distinguishable from healthy donors with an optimal cutoff of 52.81 pg/mL, yielding a sensitivity of 96% and specificity of 58.3% (AUC = 0.72). Conclusion: Serum CALR is significantly elevated in patients with PDAC, BC, and CRC compared to healthy individuals and demonstrates strong diagnostic accuracy. These findings identify CALR as a promising noninvasive biomarker for cancer detection and justifies future validation studies assessing combinatorial biomarker panels.