Oncotarget

Research Papers:

Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library

Sohei Kobayashi, Takaki Hiwasa, Takahiro Arasawa, Akiko Kagaya, Sayaka Ishii, Hideaki Shimada, Masaaki Ito, Masae Suzuki, Masayuki Kano, Bahityar Rahmutulla, Kouichi Kitamura, Yuji Sawabe, Hideo Shin, Masaki Takiguchi, Fumio Nomura, Hisahiro Matsubara and Kazuyuki Matsushita _

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Oncotarget. 2018; 9:18559-18569. https://doi.org/10.18632/oncotarget.24963

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Abstract

Sohei Kobayashi1,2, Takaki Hiwasa3, Takahiro Arasawa1,3, Akiko Kagaya3,4, Sayaka Ishii1,3, Hideaki Shimada5, Masaaki Ito5, Masae Suzuki1,3, Masayuki Kano1, Bahityar Rahmutulla6, Kouichi Kitamura2,7, Yuji Sawabe2, Hideo Shin8, Masaki Takiguchi3, Fumio Nomura9, Hisahiro Matsubara1 and Kazuyuki Matsushita2

1Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

2Department of Laboratory Medicine & Division of Clinical Genetics and Proteomics, Chiba University Hospital, Chiba 260-8670, Japan

3Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

4Clinical Research Center, Chiba University Hospital, Chiba 260-8670, Japan

5Department of Gastroenterological Surgery, School of Medicine, Toho University, Tokyo 143-8541, Japan

6Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

7Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

8Department of Neurosurgery, Higashi Funabashi Hospital, Chiba 274-0065, Japan

9Divisions of Clinical Mass Spectrometry and Clinical Genetics, Chiba University Hospital, Chiba 260-8670, Japan

Correspondence to:

Kazuyuki Matsushita, email: [email protected]

Keywords: cancer-testis antigen; SEREX; esophageal squamous cell carcinoma; AlphaLISA; gastrointestinal cancers

Received: December 27, 2017     Accepted: March 07, 2018     Published: April 06, 2018

ABSTRACT

The present study was planned to identify novel serum antibody markers for digestive organ cancers. We have used screening by phage expression cloning and identified novel fourteen antigens in this experiment. The presence of auto-antibodies against these antigens in serum specimens was confirmed by western blotting. As for auto-antibodies against fourteen antigens, AlphaLISA (amplified luminescence proximity homogeneous assay) assay was performed in the sera of gastrointestinal cancers patients to confirm the results. Serum antibody levels against these fourteen recombinant proteins as antigens between healthy donors (HD) and esophageal squamous cell carcinoma (ESCC) patients, gastric cancer (GC), or colon cancer (CC) were compared. The serum levels of all fourteen auto-antibodies were significantly higher in ESCC and GC than those of HD. Among those auto-antibodies, except ECSA2 and CCNL2, were also detected significantly higher levels in CC than those of HD. Receiver operating curve (ROC) revealed similar results except CCNL2 in CC. AUC values calculated by ROC were higher than 0.7 in auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, HS3ST1, TUBA1B, TACSTD2, AKR1C3, BAMBI, DCAF15 in ESCC, auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, TACSTD2, AKR1C3, BAMBI, DCAF15 in GC, and auto-antibodies against TPI1, HOOK2, PUF60 in CC. AUC of the combination of HOOK2 and anti-p53 antibodies in ESCC was observed to be as high as 0.8228. Higher serum antibody levels against ten antigens could be potential diagnostic tool for ESCC. Higher serum antibody levels against eight antigens could be potential diagnostic tool for GC, and serum antibody levels against three antigens could be potential diagnostic tool for CC.


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