Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma

Abstract

AIMTo construct a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis with high efficiency.METHODSDifferentially expressed lncRNAs (DELs) between HCC specimens and peritumor liver specimens were identified using the edgeR package to analyze The Cancer Genome Atlas (TCGA) LIHC dataset. Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival (OS) in a training set. These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model. Those lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula. The prognostic value of this formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lncRNAs in the signature.RESULTSBased on lncRNA expression profiling of 370 HCC patients from the TCGA database, we constructed a 5-lncRNA signature (AC015908.3, AC091057.3, TMCC1-AS1, DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis. HCC patients with high-risk scores based on the expression of the 5 lncRNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups. Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lncRNAs was independent of clinicopathological parameters. A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lncRNA signature showed improved prognostic power compared with the other two signatures. Functional enrichment analysis indicated that the 5 lncRNAs were potentially involved in metabolic processes, fibrinolysis and complement activation.CONCLUSIONOur present study constructed a 5-lncRNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.

RETRACTED: Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor

“…The overall survival and progression-free survival of bladder cancer patients with high FOXD2-AS1 expression is shorter than that of bladder cancer patients with low FOXD2-AS1 expression (Su et al, 2018). Overexpressed FOXD2-AS1 is observed in multiple other types of human cancer, including hepatocellular carcinoma (Chang et al, 2018;Zhao et al, 2018;Xu et al, 2019), glioma (Ni et al, 2019), thyroid cancer Jiang et al, 2019;Liu et al, 2019), cutaneous melanoma (Ren et al, 2019), colorectal cancer (Zhu et al, 2018), esophageal squamous cell carcinoma (Bao et al, 2018), and non-small cell lung cancer (Rong et al, 2017). Nevertheless, FOXD2-AS1 expression status in cervical cancer has been unknown and warrants investigation.…”

“…A knockdown of FOXD2-AS1 inhibits papillary thyroid cancer cell proliferation, migration, invasion, the cancer stem cell-like phenotype, and anoikis resistance in vitro; promotes apoptosis; and hinders tumorigenesis in vivo Jiang et al, 2019;Liu et al, 2019). In hepatocellular carcinoma, silencing of FOXD2-AS1 expression suppresses cell proliferation, colony formation, metastasis, and epithelial-mesenchymal transition; induces cell cycle arrest at the G0-G1 transition; and decreases tumor growth and metastasis in vivo (Chang et al, 2018;Zhao et al, 2018;Xu et al, 2019). FOXD2-AS1 also exerts oncogenic actions on carcinogenesis including progression of bladder cancer (Su et al, 2018), glioma (Ni et al, 2019), cutaneous melanoma (Ren et al, 2019), colorectal cancer (Zhu (Bao et al, 2018), and non-small cell lung cancer (Rong et al, 2017).…”

“…FOXD2-AS1 is dysregulated in multiple types of human cancer, and its dysregulation is involved in the modulation of various tumor-associated biological processes (Rong et al, 2017;Bao et al, 2018;Chang et al, 2018;Su et al, 2018;Zhang et al, 2018;Zhao et al, 2018;Zhu et al, 2018;Jiang et al, 2019;Liu et al, 2019;Ni et al, 2019;Ren et al, 2019;Xu et al, 2019). To the best of our knowledge, however, the expression status and detailed roles of FOXD2-AS1 in cervical cancer are still unknown.…”

Risk scoring based on expression of long non‑coding RNAs can effectively predict survival in hepatocellular carcinoma patients with or without fibrosis

“…Several previous studies have also constructed risk scoring systems to predict the prognosis of patients with HCC (24)(25)(26)(27)(28)(29)(30)(31). However, those risk scoring systems were based on DElncRNAs between HCC and normal samples, while the risk scoring systems in the present study are based on the DElncRNAs between HCC Table IX.…”

lncRNA HAND2-AS1 Inhibits Liver Cancer Cell Proliferation and Migration by Upregulating SOCS5 to Inactivate the JAK-STAT Pathway

“…3,4 Besides, patients are also in imminent danger of a devastatingly poor, 5-year survival rate. 5 Emphasis placed on unraveling the regulatory mechanism of hepatocarcinogenesis might be conducive to shifting dismal clinical outcomes to favorable ones in liver cancer patients.…”