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Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay

机译:酶联免疫吸附法分析着丝粒蛋白F自身抗体与癌症的相关性

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Background Centromere protein-F (CENP-F) is a large nuclear protein of 367?kDa, which is involved in multiple mitosis-related events such as proper assembly of the kinetochores, stabilization of heterochromatin, chromosome alignment and mitotic checkpoint signaling. Several studies have shown a correlation between CENP-F and cancer, e.g. the expression of CENP-F has been described to be upregulated in cancer cells. Furthermore, several studies have described a significant correlation between the expression of autoantibodies to CENP-F and cancer. Methods Autoantibodies to CENP-F were detected in a small number of samples during routine indirect immunofluorescence (IIF) analysis for anti-nuclear antibodies (ANA) using HEp-2 cells as substrate. Using overlapping synthetic peptides covering a predicted structural maintenance of chromosomes (SMC) domain, we developed an enzyme-linked immunosorbent assay ( ELISA ) for detection of CENP-F antibodies. Results Analyzing the reactivity of the sera positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed that autoantibodies to several peptides correlate with the presence of antibodies to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression specific for malignant cancer patients to five peptides was found (A9, A12, A14, A16, A27). These antibodies to CENP-F in clinical samples submitted for ANA analysis were found to have a positive predictive value for cancer of 50%. Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to increase as a function of time from diagnosis. Conclusion These results conform to previous findings that approximately 50% of those patients clinically tested for ANA analyses who express CENP-F antibodies are diagnosed with cancer, confirming that these antibodies may function as circulating tumor markers. Thus, a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying individuals with a potential cancer.
机译:背景着丝粒蛋白F(CENP-F)是一种367?kDa的大核蛋白,与多种与有丝分裂有关的事件有关,例如动植物的正确装配,异染色质的稳定,染色体比对和有丝分裂检查点信号传导。几项研究表明CENP-F与癌症之间存在相关性,例如已经描述CENP-F的表达在癌细胞中被上调。此外,一些研究已经描述了针对CENP-F的自身抗体的表达与癌症之间的显着相关性。方法在以HEp-2细胞为底物的常规间接免疫荧光(IIF)分析抗核抗体(ANA)期间,在少量样品中检测到CENP-F自身抗体。我们使用覆盖了预测的染色体结构维持结构(SMC)的重叠合成肽,开发了用于检测CENP-F抗体的酶联免疫吸附测定(ELISA)。结果分析CEIF-F抗体的IIF阳性血清对重叠的CENP-F肽的反应性,我们发现针对几种肽的自身抗体与CENP-F抗体的存在和癌症诊断相关,因为CENP-F升高发现了针对恶性肿瘤患者的针对五个肽的特异性抗体表达(A9,A12,A14,A16,A27)。在提交给ANA分析的临床样本中,这些针对CENP-F的抗体被发现对癌症的阳性预测值为50%。此外,与癌症相关的CENP-F抗体的表达似乎从诊断开始就随时间增加。结论这些结果与以前的发现相符,在临床上经ANA分析临床测试的表达CENP-F抗体的患者中约有50%被诊断出患有癌症,从而证实这些抗体可以作为循环肿瘤标志物。因此,专注于SMC结构域的基于肽的CENP-F ELISA可能有助于鉴定患有潜在癌症的个体。

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