Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients

Sohei Kobayashi,Takaki Hiwasa,Sachio Tsuchida,Yuji Komukai,Tyuji Hoshino,Hideaki Shimada,Kazuyuki Matsushita,Fumio Nomura,Hisahiro Matsubara,Tomoaki Tanaka,Bahityar Rahmutulla,Mamoru Satoh

doi:10.18632/oncotarget.12696

Abstract

Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients. Anti-FIRs antibodies were surely detected in the preoperative sera of 28 colorectal cancer patients (32.2% of positive rates), and the detection rate was significantly higher than that in healthy control sera (Mann–Whitney U test, p < 0.01). The level of anti-FIRs antibodies significantly decreased after the operation (p < 0.01). Anti-FIRs antibodies were detected in the sera of early-stage and/or recurrent colon cancer patients in which anti-p53 antibodies, CEA, and CA19-9 were not detected as well as in the sera of other cancer patients. Furthermore, the area under the curve of receiver operating characteristic for anti-FIRs antibodies was significantly larger (0.85) than that for anti-p53 antibodies or CA19-9. In conclusions, the combination of anti-FIRs antibodies with other clinically available tumor markers further improved the specificity and accuracy of cancer diagnosis.

Highlights

A recent study reported that the detection of antiPUF60, poly(U)-binding-splicing factor, auto-antibodies in dermatomyositis and Sjogren’s syndrome, indicating it reflects the immune responses of the diseases [1]
These results strongly suggested that far-upstream element-binding protein-interacting repressor (FIR)/FIRΔexon2 antibodies were present in the sera of colorectal cancer patients
The representative pictures of dot blot assay indicated that FIR/FIRΔexon2 is present as an antigen in the sera of colorectal cancer patients (Supplementary Figure S2)

Summary

Introduction

A recent study reported that the detection of antiPUF60, poly(U)-binding-splicing factor, auto-antibodies in dermatomyositis and Sjogren’s syndrome, indicating it reflects the immune responses of the diseases [1]. It is natural that anti-FIR (PUF60) antibodies could be detected in the sera of cancer www.impactjournals.com/oncotarget patients as well as in dermatomyositis and Sjogren’s syndrome. The significance of anti-FIR (PUF60) antibodies remains obscure in malignant complications of dermatomyositis or Sjogren’s syndrome. FUSE is located 1.5 kb upstream of the c-myc promoter P1 and recognized by FUSE-binding protein (FBP). FBP is a transcription factor that stimulates c-myc expression through FUSE [10,11,12]. Anti-FIRs antibodies potentially reflect c-myc activation in auto-immune diseases and cancers

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Conclusion