Hepatology International

, Volume 13, Issue 6, pp 715–725 | Cite as

Clinical and morpho-molecular classifiers for prediction of hepatocellular carcinoma prognosis and recurrence after surgical resection

  • Xiuming Zhang
  • Yanfeng Bai
  • Lei Xu
  • Buyi Zhang
  • Shi Feng
  • Liming Xu
  • Han Zhang
  • Linjie Xu
  • Pengfei Yang
  • Tianye Niu
  • Shusen ZhengEmail author
  • Jimin LiuEmail author
Original Article



Approximately 50% hepatocellular carcinoma (HCC) patients die within 5 year after surgical resection. The present staging systems do not fully allow to accurately predict the HCC prognosis and recurrence. This study aimed to identify clinicopathological characteristics and molecular markers to establish classifiers to predict the 5-year overall survival (OS) and the 3-year recurrence in HCC patients post-operatively.


We enrolled 647 HCC patients from two institutions, underwent surgical resection and divided the patients into one training and two validation cohorts. Clinicopathologic characteristics and tumor protein expression of 29 biomarkers by immunohistochemical (IHC) analysis were used to develop and validate a prognostic and a recurrent classifier, using the maximum relevance minimum redundancy algorithm jointly with the multivariable regression method.


The prognostic classifier distinguished HCC patients into high- and low-probability survival groups with significant differences in 5-year OS rate in all three cohorts (training cohort: 57.36% vs. 22.97%; p < 0.0001; internal validation cohort: 61.90% vs. 28.85%; p < 0.0001; independent validation cohort: 64.28% vs. 22.45%; p < 0.0001). The recurrent classifier also demonstrated good discrimination in all three cohorts.


This study presented a prognostic classifier and a recurrent classifier using clinicopathologic and IHC characteristics. The developed classifiers stratified HCC patients into high- and low-probability survival or recurrent groups, which can help clinicians judge whether adjuvant therapy is beneficial post-operatively.


Hepatocellular carcinoma Prognosis Recurrence Predicting classifiers Immunomarkers 



We thank the patients who participated in this study and the support from their families.

Author contributions

XZ, YB, SZ, and JL conceived and designed the experiments. XZ, YB, BZ, LX, HZ, and LX performed all the experiments. LX, SF, PY, and TN analyzed the data. XZ, LX, and JL wrote the manuscript. All authors read and approved the final manuscript.


This study was funded by the National S&T Major Project (no. 2017ZX10203205), National High-tech R&D Program for Young Scientists by the Ministry of Science and Technology of China (Grant no. 2015AA020917), National Key Research Plan by the Ministry of Science and Technology of China (Grant no. 2016YFC0104507), Natural Science Foundation of China (NSFC Grant no. 81871351), Zhejiang Medical and Health Science and Technology Project (no. 2018KY389).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine and the Second Affiliated Hospital, Zhejiang University School of Medicine. The study was in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Patients provided written informed consent before undertaking any study-related procedures.

Supplementary material

12072_2019_9978_MOESM1_ESM.docx (262 kb)
Supplementary material 1 (DOCX 263 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  1. 1.Department of Pathology, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Institute of Translational Medicine, Zhejiang UniversityHangzhouChina
  4. 4.Department of Pathology, The Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  5. 5.Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  6. 6.NHFPC Key Laboratory of Combined Multi-organ Transplantation, The First Affiliated HospitalZhejiang UniversityHangzhouChina
  7. 7.Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesHangzhouChina
  8. 8.Department of Pathology and Molecular Medicine, Faculty of Health SciencesMcMaster UniversityHamiltonCanada

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