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To date, the useful markers of hepatocellular carcinoma (HCC) remains incompletely developed. Here, we show that annexin A2 complement alpha-fetoprotein (AFP), a widely used liver cancer marker, in the serologically surveillance and early detection of HCC. First, differentially expressed proteins in HCC were identified using a subcellular proteomic approach. Annexin A2 was then selected for further verification. It was found to be overexpressed in HCC tissues (60.7%, 136/224). Using a self-estabished sandwich enzyme-linked immunosorbent assay, we found that annexin A2 significantly increased in the sera of HCC (n = 175, median, 24.75ng/µl) compared with the healthy (n = 49, median, 16.69ng/µl), benign tumors (n = 19, median, 19.92ng/µl), hepatitis (n = 23, median, 6.48ng/µl) and cirrhosis (n = 51, median, 7.39ng/µl) controls and other malignant tumors (n = 87). Importantly, raised concentrations of annexin A2 were observed in 83.2% (79/95) of early stage (median, 24.32ng/µl) and 78.4% (58/74) of AFP-negative (median, 24.09ng/µl) patients. Annexin A2 alone had a better area under the receiver-operating characteristic curve (AUC = 0.79, 95% confidence interval: 0.73–0.85) in comparison with AFP (AUC = 0.73, 95% confidence interval: 0.66–0.80) in detecting of early stage HCC. Combining both markers notably improved the diagnostic efficiency of early HCC with an achieved sensitivity of 87.4%. Additionally, the expression characteristics of annexin A2 during hepatocarcinogenesis were detected in p21-HBx gene knockin transgenic mice model. The results showed that annexin A2 expression was substantially elevated in HCC-bearing mice, in accordance with the finding in human samples. In conclusion, annexin A2 may be an independent serological candidate for hepatitis B virus–related HCC, especially in the early stage cases with normal serum AFP.

ObjectiveCirculating tumor cells (CTCs) of patients with malignant tumors can be used as a prognostic marker. However, there are few relevant reports to date on esophageal squamous cell carcinoma (ESCC). Our study assesses the clinical significance of CTCs in ESCC patients.Patients and methodsCTCs were detected in 103 peripheral blood (PB) samples from 59 ESCC patients. Correlation between CTCs and clinical parameters was analyzed using the χ2 test or Fisher’s exact test. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier analysis and univariate and multivariate methods.ResultsThe CTC detection rate was 79.7% (47/59) at baseline. The frequency of CTC-positive patients increased as the disease stage advanced (88.0% in stages III–IV, 58.9% in stages I–II). CTC counts ≥0/7.5 mL of PB were correlated with the degree of tumor differentiation, tumor infiltration, and lymph node and distant metastases. Overall, the OS and PFS of patients with CTC counts ≥3 or ≥5/7.5 mL of PB before surgery were significantly shorter than those of patients with CTC counts <3 or <5/7.5 mL. Multivariate analysis showed CTC counts ≥5/7.5 mL of PB to be a strong prognostic indicator of OS (hazard ratio [HR] 12.478; 95% confidence interval [CI], 8.2–34.3; P<0.05) and PFS (HR 6.524; 95% CI, 1.2–34.3; P<0.05) in ESCC patients. Patients in whom CTCs changed from positive at baseline to a negative value after surgery had an excellent prognosis.ConclusionCTCs might serve as a reference indicator for the prognosis and monitoring of disease progression and treatment effects in ESCC.

The new extraction method based on the nanomaterial is quick and efficient. The cancer-associated protein TGM2 can be secreted through an exosome-mediated non-classical secretion pathway, and it may be a valuable tumor marker.

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