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Poster Display session 3

1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Yongcong Yan

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

Y. Yan, K. Mao, P. Huang, J. Wang, Z. Xiao

Author affiliations

  • Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120 - Guangzhou/CN

Resources

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Abstract 1573

Background

Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, with a poor long-term prognosis worldwide. The functional deregulations of global transcriptome were associated with the genesis and development of HCC. However, reliable molecular signatures predicting overall survival (OS) lacks of systematic research and validation.

Methods

A total of 519 postoperative HCC patients were included. We built an interactive and visual competing endogenous RNA (ceRNA) network from The Cancer Genome Atlas (TCGA) database. The prognostic signature was established with the least absolute shrinkage and selection operator (LASSO) algorithm. Multivariate Cox regression analysis and subgroup analysis was used to screen for independent prognostic factors. A time-dependent ROC curve analysis was performed to compare predictive value of the prognostic signature. The robustness of the prognostic signature was validated in validation cohorts.

Results

There were 39 differentially expressed mRNAs (DEmRNAs), 83 differentially expressed lncRNAs and 20 differentially expressed miRNAs involved in the ceRNA network. Twenty DEmRNAs were found to be significantly associated with OS. We identified a 4-gene signature (PBK, CBX2, CLSPN and CPEB3) using LASSO regression in the training set. Patients in the high-score group exhibited worse survival than those in the low-score group (HR = 2.444, P = 0.0004), and median OS was significantly shorter in the high-score group than in the low-score group (1005 days versus 2456 days). The 4-gene signature was an independent prognostic factor in multivariate Cox regression and subgroup analysis, particularly for patients with serum AFP ≥ 20 ng/ml. The results were validated in internal validation set (P = 0.0057) and two external validation cohorts (HR = 1.505 and 2.626). The signature (AUCs of one, two, three years were 0.716, 0.726, 0.714, respectively) showed high prognostic accuracy.

Conclusions

We constructed a novel lncRNA-miRNA-mRNA ceRNA network for HCC based on genome-wide analysis. Then we identified a 4-gene signature as a new candidate therapeutic decision marker that yields great promise in the prediction of HCC OS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Sun Yat-Sen University.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.

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