Serum Carboxypeptidase Activity and Genotype-Stratified CA19-9 to Detect Early-Stage Pancreatic Cancer,Clinical Gastroenterology and Hepatology

当前位置： X-MOL 学术 › Clin. Gastroenterol. Hepatol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Serum Carboxypeptidase Activity and Genotype-Stratified CA19-9 to Detect Early-Stage Pancreatic Cancer
Clinical Gastroenterology and Hepatology ( IF 11.6 ) Pub Date : 2021-10-12 , DOI: 10.1016/j.cgh.2021.10.008
Haruyoshi Tanaka ₁ , Koji Tamura ₁ , Toshiya Abe ₁ , Takeichi Yoshida ₁ , Anne Macgregor-Das ₁ , Mohamad Dbouk ₁ , Amanda L Blackford ₂ , Michael Borges ₃ , Anne Marie Lennon ₄ , Jin He ₃ , Richard Burkhart ₃ , Marcia Irene Canto ₅ , Michael Goggins ₆

Affiliation

Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.

Background and Aims

Serum diagnostic markers of early-stage pancreatic ductal adenocarcinoma (PDAC) are needed, especially for stage I disease. As tumors grow and cause pancreatic atrophy, markers derived from pancreatic parenchyma such as serum carboxypeptidase A (CPA) activity lose diagnostic performance. We evaluated, with CA19-9, serum CPA as a marker of early pancreatic cancer.

Methods

Serum CPA activity levels were measured in 345 controls undergoing pancreatic surveillance, divided into 2 sets, set 1 being used to establish a reference range. Variants within the CPA1 locus were sought for their association with pancreatic CPA1 expression to determine if such variants associated with serum CPA levels. A total of 190 patients with resectable PDAC were evaluated.

Results

Among controls, those having 1 or more minor alleles of CPA1 variants rs6955723 or rs2284682 had significantly higher serum CPA levels than did those without (P = .001). None of the PDAC cases with pancreatic atrophy had an elevated CPA. Among 122 PDAC cases without atrophy, defining serum CPA diagnostic cutoffs by a subject’s CPA1 variants yielded a diagnostic sensitivity of 18% at 99% specificity (95% confidence interval [CI], 11.7–26) (vs 11.1% sensitivity using a uniform diagnostic cutoff); combining CPA with variant-stratified CA19-9 yielded a sensitivity of 68.0% (95% CI, 59.0–76.2) vs 63.1% (95% CI, 53.9– 71.7) for CA19-9 alone; and among stage I PDAC cases, diagnostic sensitivity was 51.9% (95% CI, 31.9–71.3) vs 37.0% (95% CI, 19.4–57.6) for CA19-9 alone. In the validation control set, the variant-stratified diagnostic cutoff yielded a specificity of 98.2%.

Conclusion

Serum CPA activity has diagnostic utility before the emergence of pancreatic atrophy as a marker of localized PDAC, including stage I disease.

中文翻译：

血清羧肽酶活性和基因型分层 CA19-9 用于检测早期胰腺癌

背景和目标

需要早期胰腺导管腺癌 (PDAC) 的血清诊断标志物，尤其是 I 期疾病。随着肿瘤生长并导致胰腺萎缩，来自胰腺实质的标记物，例如血清羧肽酶 A (CPA) 活性，会失去诊断性能。我们使用 CA19-9 评估血清 CPA 作为早期胰腺癌的标志物。

方法

测量了 345 名接受胰腺监测的对照者的血清 CPA 活性水平，将其分为 2 组，第 1 组用于建立参考范围。寻找CPA1基因座内的变异与胰腺CPA1表达的关联，以确定这些变异是否与血清 CPA 水平相关。共有 190 名可切除 PDAC 患者接受了评估。

结果

在对照组中，具有 1 个或多个CPA1变体 rs6955723 或 rs2284682 次要等位基因的人的血清 CPA 水平显着高于不具有 CPA1 变体的人 ( P = .001)。患有胰腺萎缩的 PDAC 病例中没有一个 CPA 升高。在 122 例无萎缩的 PDAC 病例中，通过受试者的CPA1变异定义血清 CPA 诊断临界值，在 99% 特异性下获得了 18% 的诊断灵敏度（95% 置信区间 [CI]，11.7–26）（而使用统一诊断的灵敏度为 11.1%）隔断）;将 CPA 与变异分层 CA19-9 相结合产生的敏感性为 68.0% (95% CI, 59.0–76.2)，而单独使用 CA19-9 则为 63.1% (95% CI, 53.9–71.7)；在 I 期 PDAC 病例中，单独使用 CA19-9 的诊断敏感性为 51.9% (95% CI, 31.9–71.3) vs 37.0% (95% CI, 19.4–57.6)。在验证对照集中，变异分层诊断截止值的特异性为 98.2%。