Annals of Surgical Oncology

, Volume 25, Issue 6, pp 1686–1694 | Cite as

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

  • Xiao-Lu Ma
  • Mi Jiang
  • Ying Zhao
  • Bei-Li Wang
  • Min-Na Shen
  • Yan Zhou
  • Chun-Yan Zhang
  • Yun-Fan Sun
  • Jian-Wen Chen
  • Bo Hu
  • Zi-Jun Gong
  • Xin Zhang
  • Ya Cao
  • Bai-Shen Pan
  • Jian Zhou
  • Jia Fan
  • Xin-Rong YangEmail author
  • Wei GuoEmail author
Hepatobiliary Tumors



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.



This study was supported by grants from the National Key Research and Development Program of China (2016YFF01400 and 2016YFC0902400), the National High Technology Research and Development Program (863 Program) of China (2015AA020401), the State Key Program of National Natural Science of China (81530077), the National Natural Science Foundation of China (81472676, 81572823, 81602543, 81602581, 81572064, 87172263 and 81672839), the Projects from the Shanghai Science and Technology Commission (14DZ1940300, 14411970200, 14140902301 and 16411952100), the Projects from Shanghai Municipal Commission of Health and Family Planning (201540052, and M20140189), and the Key Developing Disciplines of Shanghai Municipal Commission of Health and Family Planning (2015ZB0201).


The authors declare that there are no conflicts of interest to disclose regarding funding from industrial sources or other disclosures with respect to this study.

Supplementary material

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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Xiao-Lu Ma
    • 1
  • Mi Jiang
    • 3
  • Ying Zhao
    • 1
  • Bei-Li Wang
    • 1
  • Min-Na Shen
    • 1
  • Yan Zhou
    • 1
  • Chun-Yan Zhang
    • 1
  • Yun-Fan Sun
    • 2
  • Jian-Wen Chen
    • 2
  • Bo Hu
    • 2
  • Zi-Jun Gong
    • 2
  • Xin Zhang
    • 2
  • Ya Cao
    • 4
  • Bai-Shen Pan
    • 1
  • Jian Zhou
    • 2
  • Jia Fan
    • 2
  • Xin-Rong Yang
    • 2
    Email author
  • Wei Guo
    • 1
    Email author
  1. 1.Department of Laboratory MedicineZhongshan Hospital, Fudan UniversityShanghaiChina
  2. 2.Department of Liver Surgery, Liver Cancer InstituteZhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationShanghaiChina
  3. 3.Department of Blood TransfusionZhongshan HospitalShanghaiChina
  4. 4.Cancer Research InstituteXiangya School of Medicine, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationChangshaChina

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