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
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract