Research Papers:

Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors

Koji Hontani, Takahiro Tsuchikawa _, Takaki Hiwasa, Toru Nakamura, Takashi Ueno, Toshihiro Kushibiki, Mizuna Takahashi, Kazuho Inoko, Hironobu Takano, Satoshi Takeuchi, Hirotoshi Dosaka-Akita, Masaki Kuwatani, Naoya Sakamoto, Yutaka Hatanaka, Tomoko Mitsuhashi, Hideaki Shimada, Toshiaki Shichinohe and Satoshi Hirano

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Oncotarget. 2017; 8:106206-106221. https://doi.org/10.18632/oncotarget.22175

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Koji Hontani1, Takahiro Tsuchikawa1, Takaki Hiwasa2, Toru Nakamura1, Takashi Ueno1, Toshihiro Kushibiki1, Mizuna Takahashi1, Kazuho Inoko1, Hironobu Takano1, Satoshi Takeuchi3, Hirotoshi Dosaka-Akita3, Masaki Kuwatani4, Naoya Sakamoto4, Yutaka Hatanaka5, Tomoko Mitsuhashi5, Hideaki Shimada6, Toshiaki Shichinohe1 and Satoshi Hirano1

1Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

2Department of Biochemistry and Genetics, Chiba University, Chuo Ku, Chiba 260-8670, Japan

3Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

4Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

5Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

6Department of Surgery, School of Medicine, Toho University, Ota-ku, Tokyo 143-8541, Japan

Correspondence to:

Takahiro Tsuchikawa, email: [email protected]

Keywords: pancreatic neuroendocrine tumors; SEREX; biomarker; prognostic factor; EID3

Received: May 30, 2017     Accepted: October 14, 2017     Published: October 31, 2017


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.

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