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06.04.2018 | Hepatobiliary Tumors | Ausgabe 6/2018

Annals of Surgical Oncology 6/2018

Application of Serum Annexin A3 in Diagnosis, Outcome Prediction and Therapeutic Response Evaluation for Patients with Hepatocellular Carcinoma

Annals of Surgical Oncology > Ausgabe 6/2018
MM Xiao-Lu Ma, BSM Mi Jiang, BSM Ying Zhao, PhD Bei-Li Wang, BSM Min-Na Shen, MM Yan Zhou, MM Chun-Yan Zhang, PhD Yun-Fan Sun, PhD Jian-Wen Chen, PhD Bo Hu, PhD Zi-Jun Gong, PhD Xin Zhang, PhD Ya Cao, MD Bai-Shen Pan, PhD, MD Jian Zhou, PhD, MD Jia Fan, PhD, MD Xin-Rong Yang, PhD Wei Guo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1245/​s10434-018-6402-0) contains supplementary material, which is available to authorized users.
Xiao-Lu Ma, Mi Jiang, and Ying Zhao contributed equally to this work.



Annexin A3 (ANXA3) could induce progression of hepatocellular carcinoma (HCC) via promoting stem cell traits of CD133-positive cells. Moreover, serum ANXA3 showed preliminary diagnostic potential, however further validation was required. Meanwhile, the prognostic value of ANXA3 remained elusive. The present study aimed to validate diagnostic performance and further systematically investigate the prognostic value of serum ANXA3.


Serum ANXA3 of 368 HCC patients was determined by enzyme-linked immunosorbent assay (ELISA); 295 of these patients underwent resection and 73 underwent transcatheter arterial chemoembolization (TACE). Diagnostic performance of ANXA3 was evaluated by receiver operating characteristic (ROC) analysis, and the prognostic value was evaluated by Cox regression and Kaplan–Meier analysis. To evaluate the relationship between serum ANXA3 and circulating CD133 mRNA-positive tumor cells (CD133mRNA+ CTCs), real-time polymerase chain reaction was conducted in 69 patients who underwent resection.


Serum ANXA3 provided greater diagnostic performance than α-fetoprotein (area under the curve [AUC] 0.869 vs. 0.782), especially in early diagnosis (AUC 0.852 vs. 0.757) and discriminating HCC from patients at risk (0.832 vs. 0.736). Pretreatment ANXA3 was an independent predictor of tumor recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, p = 0.002)/progression (HR 1.88, 95% CI 1.04–3.43, p = 0.038) and survival (resectable: HR 2.26, 95% CI 1.44–3.56, p = 0.001; unresectable: HR 2.08, 95% CI 1.10–4.05, p = 0.025), and retained its performance in low-recurrence-risk subgroups. Specifically, dynamic changes of ANXA3-positive status was associated with worse prognosis. ANXA3 was positively correlated with CD133mRNA+ CTCs (r = 0.601, p < 0.001). In patients with detectable CD133mRNA+ CTC, high ANXA3 was positively associated with a higher risk of recurrence and shorter overall survival.


Serum ANXA3 shows promise as a biomarker for diagnosis, outcome prediction, and therapeutic response evaluation in patients with HCC.

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