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.
Resources from the same session
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract