Abstract
Pancreatic neuroendocrine tumors (pNETs) are relatively rare heterogenous tumors, comprising only 1–2% of all pancreatic neoplasms. The majority of pNETs are non-functional tumors (NF-pNETs) that do not produce hormones, and as such, do not cause any hormone-related symptoms. As a result, these tumors are often diagnosed at an advanced stage because patients do not present with specific symptoms. Although tumor markers are used to help diagnosis and predict some types of cancers, chromogranin A, a widely used tumor marker of pNETs, has significant limitations. To identify novel NF-pNET-associated antigens, we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified five tumor antigens (phosphatase and tensin homolog, EP300-interacting inhibitor of differentiation 3 [EID3], EH domain-containing protein 1, galactoside-binding soluble 9, and BRCA1-associated protein). Further analysis using the AlphaLISA® immunoassay to compare serum antibody levels revealed that antibody levels against the EID3 antigen was significantly higher in the patient group than in the healthy donor group (n = 25, both groups). In addition, higher serum anti-EID3 antibody levels in NF-pNET patients correlated with shorter disease-free survival. The AUC calculated by ROC analysis was 0.784 with moderate diagnostic accuracy. In conclusion, serum anti-EID3 antibody levels may be useful as a tumor marker for prediction of tumor recurrence in NF-pNETs.
Highlights
Pancreatic neuroendocrine tumors are relatively rare tumors originating from neuroendocrine cells, which have attracted growing attention in recent years due to their increasing prevalence worldwide [1, 2]. pNETs can be classified as functional pNETs (F-pNETs) and nonfunctional pNETs (NF-pNETs) depending upon the presence of hormone-related symptoms
We examined the accuracy of serum anti-EP300 interacting inhibitor of differentiation 3 (EID3) Ab levels and serum Chromogranin A (CgA) levels to serve as a tumor marker for NF-pNETs
The purpose of this study was to identify novel serum antibodies in patients with NF-pNETs using SEREX screening, with patient sera as the detection platform
Summary
Pancreatic neuroendocrine tumors (pNETs) are relatively rare tumors originating from neuroendocrine cells, which have attracted growing attention in recent years due to their increasing prevalence worldwide [1, 2]. pNETs can be classified as functional pNETs (F-pNETs) and nonfunctional pNETs (NF-pNETs) depending upon the presence of hormone-related symptoms. F-pNETs are often diagnosed at an early stage due to symptoms such as insulinoma related to hypoglycemia, gastrinoma, and gastrointestinal carcinoid tumors. Patients with NF-pNETs do not present with specific symptoms, and are typically diagnosed at an advanced stage [3]. Because there are few effective tumor markers for pNETs, the evaluation of anti-tumor therapy efficacy and screening of recurrence are mainly performed by imaging tests. Chromogranin A (CgA) is currently used as a tumor marker for pNETs in western populations; its value is influenced by various factors including comorbid conditions or medications and lack of assay standardization [4,5,6]. There is a need to identify novel tumor markers that can aid with the detection and management of pNETs
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