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.
Clin Gastroenterol Hepatol. 2022 Oct;20(10):2267-2275.e2. doi: 10.1016/j.cgh.2021.10.008. Epub 2021 Oct 12.
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.
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.
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%.
Serum CPA activity has diagnostic utility before the emergence of pancreatic atrophy as a marker of localized PDAC, including stage I disease.
需要寻找血清早期胰腺导管腺癌（PDAC）的诊断标志物，尤其是针对Ⅰ期疾病。随着肿瘤的生长并导致胰腺萎缩，来源于胰腺实质的标志物（如血清羧肽酶 A [CPA] 活性）丧失了诊断性能。我们用 CA19-9 评估了血清 CPA 作为早期胰腺癌标志物的作用。
在接受胰腺监测的 345 例对照者中测量了血清 CPA 活性水平，分为 2 组，第 1 组用于建立参考范围。为了确定是否与血清 CPA 水平相关，我们研究了 CPA1 基因座内的变异与胰腺 CPA1 表达的关联。共评估了 190 例可切除的 PDAC 患者。
在对照者中，与不携带 rs6955723 或 rs2284682 等 CPA1 变异的个体相比，携带 1 个或更多该变异的个体的血清 CPA 水平显著更高（P =.001）。无胰腺萎缩的 PDAC 病例均未出现 CPA 升高。在 122 例无萎缩的 PDAC 病例中，根据个体的 CPA1 变异确定血清 CPA 诊断切点，其诊断敏感性为 99%特异性时为 18%（95%置信区间[CI]，11.7-26）（使用统一诊断切点时为 11.1%）；将 CPA 与变异分层的 CA19-9 相结合，对 CA19-9 单独检测时的敏感性为 68.0%（95%CI，59.0-76.2）（95%CI，53.9-71.7）；在Ⅰ期 PDAC 病例中，与 CA19-9 单独检测时的敏感性为 51.9%（95%CI，31.9-71.3）（95%CI，19.4-57.6）。在验证对照组中，该变异分层诊断切点的特异性为 98.2%。
血清 CPA 活性作为局部 PDAC（包括Ⅰ期疾病）的标志物，在胰腺萎缩出现之前具有诊断效用。
