Abstract
Hepatocellular carcinoma (HCC) is a worldwide prevalent cancer with an exremely poor prognosis. Detection of serum α-fetoprotein (AFP) and liver imaging techniques are the conventional methods used clinically for the identification of this malignancy. However, these techniques are not reliable for early diagnosis, and particularly the sensitivity and specificity of AFP in HCC diagnosis are not optimal. Therefore, there is an urgent need for the development of more sensitive and specific methods that can improve AFP quantification in the early detection of HCC. In the present study, autoantibody responses to nucleophosmin (NPM1) in HCC patients were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting and indirect immunofluorescence. Immunohistochemistry (IHC) with tissue array slides was also performed to analyze protein expression of NPM1 in HCC and control tissues. The prevalence of autoantibodies against NPM1 was 22.4% (17/76) in HCC, which was significantly higher than that in sera from patients with liver cirrhosis (LC), chronic hepatitis (CH) and systemic lupus erythematosus (SLE) (P<0.01). The average titer of autoantibodies against NPM1 in HCC sera was higher compared to that in LC, CH, SLE and normal human sera (NHS) (P<0.01). In addition, anti-NMP1 autoantibodies were detected in sera from several HCC patients with serial bleeding samples. A stronger reactive band corresponding to NMP1 was visualized in the western blot analyses, utilizing sera from patients 3–6 months before the clinical diagnosis of HCC. Our data indicate that NPM1 and the anti-NPM1 system may have potential as an early-stage biomarker for HCC screening and diagnosis.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common types of cancer and the third cause of cancer-related mortality worldwide
The full-length recombinant NPM1 protein was used as a coating antigen in enzyme-linked immunosorbent assay (ELISA) to screen autoantibodies against NPM1 in sera from patients with HCC, liver cirrhosis (LC), chronic hepatitis (CH), systemic lupus erythematosus (SLE) and as well as normal human sera (NHS)
Antigenic changes in cancer cells can be recognized by the immune system of patients themselves as autoantibody responses to proteins involved in malignant transformation
Summary
Hepatocellular carcinoma (HCC) is one of the most common types of cancer and the third cause of cancer-related mortality worldwide. The survival expectancy is usually no more than 6 months for HCC patients due to the lack of sensitive detection method at the early stage of cancer. Serum α-fetoprotein (AFP) is the most commonly used biomarker to detect HCC in clinical screening, its sensitivity and specificity are limited. HCC patients with small tumors or with well-to-moderately differentiated tumors may not have a high level of serum AFP. It is necessary to identify other sensitive biomarkers to ensure a more accurate HCC diagnosis. Many studies have demonstrated that tumor-associated antigens (TAAs) and antiTAA antibodies may be useful biomarkers for the diagnosis of certain types of cancer. The identification of TAAs and antiTAA antibodies may become a useful tool for HCC diagnosis, focusing on early facets of the disease
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