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    • As an essential nuclear protein associated with the centrome

    2018-10-23

    As an essential nuclear protein associated with the centromere–kinetochore complex, CENPF plays a critical role in chromosome segregation during mitosis (Dai et al., 2013). Researchers have demonstrated that CENPF is overexpressed in a wide variety of human malignancies including HCC, and CENPF is an independent prognostic factor for HCC (Dai et al., 2013). A recent study has also reported detection of autoantibodies to CENPF in HCC by screening a T7 cDNA LY335979 library (Liu et al., 2012). HSP60 is a chaperone with essential functions for cell physiology and survival, and has been reported to be involved in the pathogenesis of a number of cancers and some autoimmune disorders (Calderwood et al., 2012). HSP60 has also been shown to be present in a broad spectrum of cancers in both tissue and serum (Hamelin et al., 2011), and has been identified as a TAA in breast cancer, colorectal cancer and ovarian cancer (He et al., 2007; Bodzek et al., 2014). The autoantibodies to CENPF and HSP60 were also identified in the present study, but unlike the results of previous studies, their diagnostic value for early HCC was demonstrated through high throughput clinical evaluation. IMP-2 and CRT have been reported as TAAs of HCC and many other types of cancer by several studies (Zhang and Chan, 2002; Pekarikova et al., 2010), but not identified in the present study. However, the diagnostic value of IMP-2 for HCC was confirmed in the present study. Although there was a significant difference between autoantibody levels to CRT in HCC compared to controls, the AUC value was only 0.566, suggesting low diagnostic value for autoantibody to CRT. Another Ca-regulating protein, RGN for Ca-binding, also showed a statistically significant difference between HCC and controls, but with an AUC value of only 0.582 suggesting a similar diagnostic value as CRT. So far, there has been less analysis concerning the clinicopathological association and comparison with AFP in the studies concerning anti-TAA autoantibodies in cancer (Yau et al., 2013; Werner et al., 2015; Lacombe et al., 2014). In the present study, clinicopathological analysis demonstrated that three TAAs, CENPF, HSP60 and IMP-2 had the highest prevalence of autoantibody positivity in HCC cases with tumor stage BCLC A, well-differentiated histology and Child-Pugh grade C. Therefore, the clinicopathological analysis in the present study implies that TAAs may have value in surveillance and diagnosis of early HCC. To date, AFP is still the main serum biomarker for HCC surveillance. However, AFP does not yield satisfactory results in the early diagnosis of HCC, particularly AFP-negative HCC. It has been reported that in small hepatic tumors, AFP expression is lower, whereas AFP expression is high in large tumors (Zhao et al., 2013). The AFP level was approximately correlated with tumor size; 80% of small HCCs did not have increased levels of AFP. The sensitivity of AFP was 52% when the tumor diameter was >3cm, but decreased to 25% for tumors <3cm (Farinati et al., 2006; Zhao et al., 2013). The present study showed that several anti-TAA autoantibodies were better than AFP for the diagnosis of early HCC when analyzed with all controls, whereas the efficacy of the TAAs was similar to AFP in distinguishing early HCC from liver cirrhosis. HCCs occur generally from liver cirrhosis. Although the specificity of CENPF (37.1%) or HSP60 (50.6%) autoantibody seemed to be relatively low for the discrimination of HCC from liver cirrhosis, with autoantibody positivity to CENPF or HSP60 in 73.6% or 79.3% of AFP negative early HCC cases (see Table 5), the TAAs could be used as a complement for AFP in the diagnosis of AFP-negative early HCC to improve the detection rate of early HCC, and the combined autoantibody to TAAs with AFP could be helpful for the detection of AFP-negative early HCC. It is worthy to note that the prevalence of the above TAAs in LC patients was relatively high, suggesting their potential value in the detection of LC, and should be investigated further.