Construction and evaluation of a prognosis lncRNA model for hepatocellular carcinoma

Li, Fulei; Bai, Lu; Li, Shasha; Chen, Yanling; Xue, Xiaofei; Yu, Zujiang

doi:10.1002/jcb.29608

Cited by 7 publications

(9 citation statements)

References 49 publications

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“…To further illustrate the performance of GILncSig in our study, we recruited two recently published lncRNA signatures for survival prediction of HCC patient. Li’s study included 12-lncRNA signature (LilncSig) and Ma’s study included 4-lncRNA signature (MalncSig) [ 28 , 29 ]. For LilncSig, Li et al analyzed 12 pairs of HCC and adjacent normal mucosal tissues and identified 3900 differentially expressed lncRNAs as candidate biomarkers for the prognosis of HCC [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…Li’s study included 12-lncRNA signature (LilncSig) and Ma’s study included 4-lncRNA signature (MalncSig) [ 28 , 29 ]. For LilncSig, Li et al analyzed 12 pairs of HCC and adjacent normal mucosal tissues and identified 3900 differentially expressed lncRNAs as candidate biomarkers for the prognosis of HCC [ 28 ]. The 12-lncRNA signature was constructed using the least absolute shrinkage and selection operator (LASSO) cox regression method [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

“…To further confirm the performance in prognosis prediction of GILncSig, we recruited two recently published lncRNA signatures of survival prediction for HCC patient [ 28 , 29 ]. We found that the AUC for the GILncSig with lower number of lncRNA was higher than that of LilncSig and MalncSig, indicating our GILncSig possessed more optimized prognostic effect.…”

Section: Discussionmentioning

confidence: 99%

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Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

Huang

Liao

Tong

et al. 2021

Aging

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Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, genome instability-associated lncRNAs (GILncRNAs) and their performance in clinical prognostic significance in hepatocellular carcinoma (HCC) are rarely reported. Our study constructed a computational framework integrating somatic mutation information and lncRNA expression profiles of HCC genome and we identified 88 GILncRNAs of HCC. Function enrichment analysis revealed that GILncRNAs were involved in various metabolism processes and genome instability of cancer. A genome instability-derived lncRNA-based gene signature (GILncSig) was constructed using training set data. The performance of GILncSig for outcome prediction was validated in testing set and The Cancer Genome Atlas (TCGA) set. The multivariate cox regression analysis and stratification analysis demonstrated GILncSig could serve as an independent prognostic factor for the overall survival of HCC patients. The time-dependent Receiver Operating Characteristic (ROC) curve illustrated GILncSig outperformed two recently published lncRNA signatures for overall survival prediction. The combination of GILncSig and tumor protein p53 (TP53) mutation status exhibited better prognostic performance in survival evaluation compared to TP53 mutation status alone. AC145343.1 was further validated to be a risk factor for HCC in vitro among GILncSig . Overall, our study provided a novel approach for identification of genome instability-associated lncRNAs and established an independent risk score system for outcome prediction of HCC patients, which provided a new insight for exploring in-depth mechanism and potential therapy strategy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

Huang

Liao

Tong

et al. 2021

Aging

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“…According to previous reports, high expression levels of collagen type XXIV alpha 1 chain ( 43 ), ubiquilin 2 ( 44 ), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 ( 45 ), acyl-CoA synthetase long chain family member 4 ( 46 ) and YTH N6-methyladenosine RNA binding protein 1 ( 47 ) are associated with the progression of HCC. Another study has demonstrated that in addition to the American Joint Committee on Cancer staging system, a long non-coding RNA-based risk score is another important factor affecting the overall survival of patients with HCC ( 48 ). However, none of the above methods are currently widely used in the clinic.…”

Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-α (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase IIα. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319x10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40x10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

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“…Long non-coding RNAs (lncRNAs) are special RNA molecules without protein-coding potential and are longer than 200 nucleotides [4][5][6] . It has been reported that they are important in tumorigenesis and progression [4,[7][8][9][10][11][12][13] . For example, lncRNA MiR4435-2HG overexpression has been associated with poor prognosis in colorectal cancer (CRC) [14] .…”

Section: Read Full Licensementioning

confidence: 99%

Identification and Validation of lncRNA-Related Prognostic Signatures in Cholangiocarcinoma

Zhang

Huang

et al. 2021

Preprint

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Background and Aims: Cholangiocarcinoma (CCA), the second most common hepatobiliary cancer, is associated with poor prognosis. Therefore, there is a need to elucidate on the pathogenic mechanisms of CCA. In this study, we aimed at identifying lncRNA-related prognostic signatures for CCA through bioinformatics analysis and further validated their functions in CCA tumorigenesis and progression.Methods: The RNA-seq data of CCA were downloaded from public databases. Differentially expressed lncRNAs (DElncRNAs) were screened using R packages. Then, candidate OS- and DFS-related DElncRNAs were selected through Kaplan–Meier survival analysis. Furthermore, LASSO regression analyses were performed to establish two prognostic signatures, termed the OS and DFS signatures, respectively. Multivariate COX models and nomograms for overall survival (OS) and disease-free survival (DFS) were established based on OS/DFS signature and clinical data. Hub lncRNAs were identified and enrichment analyses performed to explore their potential functions. Finally, in vitro and in vivo models were used to validate the effects of the hub lncRNAs in CCA tumorigenesis and progression.Results: A total of 925 DElncRNAs were selected, from which six candidate OS-related lncRNAs and 15 candidate DFS-related lncRNAs were identified. The OS and DFS signatures were then established using four lncRNAs, respectively. We found that the OS signature and vascular invasion were significant independent risk factors for OS outcomes of CCA, while the DFS signature, vascular invasion and CA19-9 were significant independent risk factors for DFS outcomes of CCA. MiR4435-2HG and GAPLINC were selected as hub lncRNAs because they were included in both OS and DFS signatures. GO and KEGG enrichment analyses revealed that the two hub lncRNAs were involved in CCA tumorigenesis and progression. Finally, we constructed in vitro and in vivo models and revealed that the lncRNAs, MiR4435-2HG and GAPLINC can prompt CCA proliferation and migration in vitro and in vivo.Conclusions: The established OS and DFS signatures, which were based on DElncRNAs, are independent risk factors for OS and DFS of CCA patients, respectively. MIR4435-2HG and GAPLINC were identified as hub lncRNAs. In vitro and in vivo models revealed that MiR4435-2HG and GAPLINC can prompt CCA progression, which might be novel prognostic biomarkers and therapeutic targets for CCA.

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Construction and evaluation of a prognosis lncRNA model for hepatocellular carcinoma

Cited by 7 publications

References 49 publications

Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

Identification and Validation of lncRNA-Related Prognostic Signatures in Cholangiocarcinoma

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