Ge Luqi, Jin Tiefeng, Zhang Wanli, Zhang Zhentao, Zhang Yiwen, Hu Xiaoping, Zhang Wen, Song Feifeng, Huang Ping
Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.
Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
J Cancer Res Clin Oncol. 2023 Nov;149(15):14255-14269. doi: 10.1007/s00432-023-05241-9. Epub 2023 Aug 9.
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.
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.
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.
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.
肝细胞癌（HCC）仍然是一种高致死性恶性肿瘤，复发和转移率高。癌症干细胞（CSCs）参与肿瘤转移、复发及耐药，近年来受到广泛关注。研究表明，假基因可能调控干性以促进HCC进展，但其具体机制及对预后的影响尚不清楚。
本研究首先从癌症基因组图谱（TCGA）数据库下载HCC的临床预后信息。然后计算基于mRNA表达的HCC干性指数（mRNAsi）。我们还筛选了差异表达假基因（DEPs）并进行单因素Cox回归分析，以研究它们对HCC预后的影响。此外，进行基因组突变频率分析和加权基因共表达网络分析（WGCNA），以比较假基因和干性在促进HCC进展中的作用。最后，进行相关性分析以研究假基因调控干性促进HCC进展的潜在机制，并通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析检测可能的途径。
在此，我们揭示HCC的高干性与不良预后相关。我们在HCC中获得了31个上调和8个下调的DEPs，并筛选出CTB-63M22.1，它是HCC的一个不良预后指标。此外，CTB-63M22.1的突变频率与mRNAsi相似，并且在HCC上的作用模块与mRNAsi相似。然后我们筛选出与干性相关性最高的两种RNA结合蛋白（RBPs）LIN28B和NOP56。我们还发现它们主要富集在有丝分裂核分裂和细胞周期等生物学过程中。
总体而言，这些结果表明假基因CTB-63M22.1可能通过调控RBPs来调节癌症干性，提示CTB-63M22.1可能作为HCC的创新治疗靶点和可靠的预后标志物。
