Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case-control study

摘要

Background: Screening and early diagnosis tools are lacking for pancreatic adenocarcinoma; most patients are diagnosed with metastatic disease. Autoantibodies to tumor-associated antigens (TAAs) can be present months to years before diagnosis and hold promise as biomarkers for early detection. Methods: TAAs to pancreatic cancer autoantibodies CTDSP1 (carboxy-terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1), MAPK9 (mitogen-activated protein kinase 9), and NR2E3 (nuclear receptor subfamily 2, group E, member 3), which were identified as potentially promising biomarkers in exploratory studies, were evaluated in serum from participants (300 cases, 300 controls) in a population-based case-control pancreatic cancer study in the San Francisco Bay Area. Patients were identified through cancer registry rapid case ascertainment, newly diagnosed from 1995 to 1999 and followed up through 2008. Autoantibody levels were analyzed as continuous and grouped (quartiles) variables. Multivariable unconditional logistic regression was used to compute odds ratios (ORs) as estimates of autoantibody levels associated with disease status. Kaplan-Meier product limit estimates and multivariable Cox proportional hazards regression were used to assess autoantibody levels associated with case survival duration. Results: Cases had higher levels of CTDSP1 (P =.004), MAPK9 (P =.0002), and NR2E3 (P ≤.0001) autoantibodies than controls (fourth vs first quartile: CTDSP1 OR = 1.7, MAPK9 OR = 2.5, NR2E3 OR = 4.0). High body mass index and tobacco use were associated with levels in controls but were not statistical confounders. High CTDSP1 levels were somewhat associated with better survival (hazard ratio = 0.77, P =.07). Conclusions: Combined with previous results, this study contributes evidence that cancer-related host immune-response factors may be useful diagnostic screening tools and prognostic indicators for pancreatic cancer. Further studies are needed to critically assess the value of autoantibody panels to TAAs in diagnostic screening, prognosis, and immunotherapy of pancreatic and other cancers. Cancer 2012.