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