Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 16;20(1):887.
doi: 10.1186/s12885-020-07391-2.

Development and validation of a novel pseudogene pair-based prognostic signature for prediction of overall survival in patients with hepatocellular carcinoma

Yajuan Du  1 , Ying Gao  2
Affiliations

Development and validation of a novel pseudogene pair-based prognostic signature for prediction of overall survival in patients with hepatocellular carcinoma

Yajuan Du et al. BMC Cancer. .

Abstract

Background: There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC).

Methods: RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature.

Results: A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer.

Conclusion: The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.

Keywords: Hepatocellular carcinoma; Pseudogene pairs; Signature; Survival.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Predictor selection by LASSO algorithm. a: Parameter filter by LASSO regress algorithm used five-fold cross-validation by through minimum criteria; b: Optimal feature selection based on LASSO coefficient profile plot of 19 pseudogene pairs
Fig. 2
Fig. 2
Association between the pseudogene pair-based signature risk score and clinical parameters in the TCGA cohort
Fig. 3
Fig. 3
Time-dependent ROC curve analysis of the risk score. A cutoff point of risk score was identified as 0.509 to divide patients into two distinct groups in the TCGA cohort
Fig. 4
Fig. 4
Kaplan-Meier survival curves for patients with HCC in two distinct groups. Survival cures in the TCGA cohort (a), ICGC dataset (b), and subgroup analysis with respect to age (c, d), gender (e, f), histological grade (g, h), American Joint Committee on Cancer stage (i, j), family history (k, l), and vascular invasion (m, n)
Fig. 5
Fig. 5
The ROC curve for 1-, 3- and 5-year overall survival prediction using the pseudogene pair-based prognostic. a TCGA cohort; b ICGC cohort
Fig. 6
Fig. 6
Diagnosis value of pseudogene pair-based signature risk score in HCC and normal controls. ROC in normal tissues and HCC samples in the TCGA cohort (a) and ICGC cohort (b). ROC for stage I samples and normal tissues in the TCGA cohort (c) and ICGC cohort (d)
Fig. 7
Fig. 7
Comparison of C-index among the novel model, previously established prognostic signatures, and clinical features (age, sex, stage, grade, and their combination)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet (London, England) 2012;379(9822):1245–1255. - PubMed
    1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–2576. - PubMed
    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. - PubMed
    1. Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol. 2013;10(1):34–42. - PubMed
    1. Milligan MJ, Harvey E, Yu A, Morgan AL, Smith DL, Zhang E, Berengut J, Sivananthan J, Subramaniam R, Skoric A, et al. Global Intersection of Long Non-Coding RNAs with Processed and Unprocessed Pseudogenes in the Human Genome. Front Genet. 2016;7:26. - PMC - PubMed