Identification of potential pseudogenes for predicting the prognosis of hepatocellular carcinoma

Luqi Ge; Tiefeng Jin; Wanli Zhang; Zhentao Zhang; Yiwen Zhang; Xiaoping Hu; Wen Zhang; Feifeng Song; Ping Huang

doi:10.1007/s00432-023-05241-9

Identification of potential pseudogenes for predicting the prognosis of hepatocellular carcinoma

J Cancer Res Clin Oncol. 2023 Nov;149(15):14255-14269. doi: 10.1007/s00432-023-05241-9. Epub 2023 Aug 9.

Authors

Luqi Ge^{1

2}, Tiefeng Jin², Wanli Zhang^{1

2}, Zhentao Zhang^{1

2}, Yiwen Zhang^{2

3}, Xiaoping Hu², Wen Zhang¹, Feifeng Song^{4

5}, Ping Huang^{6

7}

Affiliations

¹ Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.
² Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
³ Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, China.
⁴ Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. songfeifeng@hmc.edu.cn.
⁵ Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, China. songfeifeng@hmc.edu.cn.
⁶ Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. huangping@hmc.edu.cn.
⁷ Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, China. huangping@hmc.edu.cn.

PMID: 37553422
DOI: 10.1007/s00432-023-05241-9

Abstract

Purpose: Hepatocellular carcinoma (HCC) remains a highly deadly malignant tumor with high recurrence and metastasis rates. Cancer stem cells (CSCs) are involved in tumor metastasis, recurrence, and resistance to drugs, which have attracted widespread attention in recent years. Research has shown that pseudogenes may regulate stemness to promote the progression of HCC, but its specific mechanisms and impact on prognosis remain unclear.

Methods: In this study, clinical prognosis information of HCC was first downloaded from The Cancer Genome Atlas (TCGA) database. Then we calculated the mRNA expression-based stemness index (mRNAsi) of HCC. We also screened the differentially expressed pseudogene (DEPs) and conducted univariate Cox regression analysis to investigate their effect on the prognosis of HCC. Further, genomic mutation frequency analysis and weighted gene co-expression network analysis (WGCNA) were performed to compare the role of pseudogenes and stemness in promoting the progression of HCC. Finally, we conducted the correlation analysis to examine the potential mechanism of pseudogenes regulating stemness to promote the progression of HCC and detected the possible pathways through the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results: Herein, we revealed that the high stemness of HCC correlated with an unfavorable prognosis. We obtained 31 up-regulated and 8 down-regulated DEPs in HCC and screened CTB-63M22.1, a poor prognostic indicator of HCC. In addition, CTB-63M22.1 had a mutation frequency similar to mRNAsi and acted in a module similar to that of mRNAsi on HCC. We then screened two RNA-binding proteins (RBPs) LIN28B and NOP56 with the highest correlation with stemness. We also discovered that they were primarily enriched in the biological process as examples of mitotic nuclear division and cell cycle.

Conclusions: Collectively, these results revealed that pseudogenes CTB-63M22.1 may regulate cancer stemness by regulating RBPs, suggesting that CTB-63M22.1 may serve as an innovative therapeutic target and a reliable prognostic marker for HCC.

Keywords: CTB-63M22.1; Differential pseudogenes; Hepatocellular carcinoma (HCC); Prognosis; Stemness; TCGA.

Abstract

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