Clinical and morpho-molecular classifiers for prediction of hepatocellular carcinoma prognosis and recurrence after surgical resection
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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.
KeywordsHepatocellular carcinoma Prognosis Recurrence Predicting classifiers Immunomarkers
We thank the patients who participated in this study and the support from their families.
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.
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.
Patients provided written informed consent before undertaking any study-related procedures.
- 9.Manghisi G, Elba S, Mossa A, Giorgio A, Aloisio V, Perrotta A, et al. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 1998;28:751–755Google Scholar