PO.CL01.19 · 临床研究

血清钙网蛋白作为一种有前景的癌症筛查生物标志物

Serum calreticulin as a promising biomarker for cancer screening

编号 2543 展板 18 时间 4/20 09:00–12:00 区域 Section 44 主讲 Jasmine Watts, No Degree

分会场 Early Detection Biomarkers 2

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作者与单位 Authors & Affiliations

Jasmine Watts¹, Lucinda Ann Hall², Lorenzo Thompson³, Jacqueline L. Mudd⁴, Steven Forsythe¹, Yuvasri Golivi², Roheena Panni⁴, William E. Gillanders⁵, Li Ding⁵, Ryan C. Fields⁶, Benjamin Larimer⁷, Rachael Guenter¹, John B. Rose²

¹Department of Surgery, University of Alabama at Birmingham, Birmingham, AL,²University of Alabama at Birmingham, Birmingham, AL,³Immunology Institute, University of Alabama at Birmingham, Birmingham, AL,⁴Department of Surgery, Washington University School of Medicine, St. Louis, MO,⁵Washington University School of Medicine, St. Louis, MO,⁶Department of Surgery, University of Rochester Medical Center, Rochester, NY,⁷Department of Radiology, University of Alabama at Birmingham, Birmingham, AL

摘要 Abstract

中文摘要

背景:钙网蛋白(CALR)是一种内质网伴侣蛋白,在细胞应激期间可易位至质膜。尽管CALR在癌症中的作用已知,但血液中CALR水平在癌症患者中尚未得到广泛研究。我们假设癌症患者血清CALR升高,可能作为一种早期检测的非侵入性生物标志物。方法:从诊断为胰腺导管腺癌(PDAC)、乳腺癌(BC)、结直肠癌(CRC)的患者以及健康供者中收集血清样本。使用RayBiotech人CALR夹心ELISA定量CALR浓度。使用Mann-Whitney U检验进行组间比较,并使用ROC分析在GraphPad Prism上评估诊断性能。结果:研究纳入了80例PDAC患者、25例BC患者、25例CRC患者和60例健康供者。CALR水平中位数(IQR)从健康个体的36.22 pg/mL(5.09-264.6)升高至PDAC患者的363.1 pg/mL(226.5-729.7)、CRC患者的182.5 pg/mL(108.1-344.0)和BC患者的584.9 pg/mL(381.2-823.4)。两两检验证实PDAC相对于健康(p<0.0001)、BC相对于健康(p<0.0001)和CRC相对于健康(p=0.0021)的CALR水平显著更高。ROC分析显示血清CALR在区分PDAC与健康个体方面具有很强的诊断潜力(AUC=0.799)。使用Youden指数确定的最佳临界值为147 pg/mL,灵敏度为89%,特异度为71.7%。区分健康供者与BC也具有统计学意义(AUC=0.844),在最佳临界值308.7 pg/mL时灵敏度为88%,特异度为73.33%。CRC也可与健康供者区分,最佳临界值为52.81 pg/mL,灵敏度为96%,特异度为58.3%(AUC=0.72)。结论:与健康个体相比,血清CALR在PDAC、BC和CRC患者中显著升高,并显示出很强的诊断准确性。这些发现将CALR确定为一种有前景的非侵入性癌症检测生物标志物,并为未来评估组合生物标志物组合的验证研究提供了理由。

查看英文原文 English abstract

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.

利益披露 Disclosure

J. Watts, None.. L. Thompson, None.. J. L. Mudd, None.. S. Forsythe, None.. R. Panni, None.. W. E. Gillanders, None.. L. Ding, None.. R. C. Fields, None.. B. Larimer, None.. R. Guenter, None.. J. B. Rose, None.

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