Kobayashi Sohei, Hoshino Tyuji, Hiwasa Takaki, Satoh Mamoru, Rahmutulla Bahityar, Tsuchida Sachio, Komukai Yuji, Tanaka Tomoaki, Matsubara Hisahiro, Shimada Hideaki, Nomura Fumio, Matsushita Kazuyuki
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan.
Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Oncotarget. 2016 Dec 13;7(50):82493-82503. doi: 10.18632/oncotarget.12696.
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.
据报道，在偶尔与恶性肿瘤相关的皮肌炎和干燥综合征患者血清中可检测到抗PUF60（聚尿苷结合剪接因子）自身抗体。PUF60与远上游元件结合蛋白相互作用阻遏物（FIR）相同，FIR是c-myc基因的转录阻遏物。在结直肠癌中，缺乏外显子2的FIR剪接变体（FIRΔexon2）作为FIR的显性负性形式过表达。在本研究中，为了揭示抗FIR（FIR/FIRΔexon2）抗体在癌症患者血清中的存在情况及其意义，对结直肠癌和其他癌症患者血清进行了检测。在28例结直肠癌患者的术前血清中确实检测到了抗FIR抗体（阳性率为32.2%），检测率显著高于健康对照血清（曼-惠特尼U检验，p<0.01）。术后抗FIR抗体水平显著降低（p<0.01）。在未检测到抗p53抗体、癌胚抗原（CEA）和糖类抗原19-9（CA19-9）的早期和/或复发性结肠癌患者血清以及其他癌症患者血清中均检测到了抗FIR抗体。此外，抗FIR抗体的受试者操作特征曲线下面积（0.85）显著大于抗p53抗体或CA19-9。总之，抗FIR抗体与其他临床可用肿瘤标志物联合使用可进一步提高癌症诊断的特异性和准确性。
