Open Access
ARTICLE
A novel nine gene signature integrates stemness characteristics associated with prognosis in hepatocellular carcinoma
XINGHONG YAO1,2,#, CHENGQUAN LU3,#, JUNYI SHEN1, WENLI JIANG1, YAN QIU1, YE ZENG1,*, LIANG LI1,*
1 Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
2 Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610041, China
3 Jinzhou City Center for Disease Control and Prevention, Jinzhou, 121000, China
* Corresponding Authors: YE ZENG. Email: ; LIANG LI. Email:
BIOCELL 2021, 45(6), 1425-1448. https://doi.org/10.32604/biocell.2021.017289
Received 28 April 2021; Accepted 26 July 2021; Issue published 01 September 2021
Abstract
Cancer stem cells (CSCs) are heterogeneous with self-renewal and differentiation ability. The mRNA expression-based stemness index (mRNAsi) described the similarity between tumor cells and CSCs, which is positively associated with the poor prognosis of cancer patients. However, the key prognostic genes related to mRNAsi in hepatocellular carcinoma (HCC) remains unclear. A 9-gene signature related to mRNAsi and HCC prognosis including
PSMG3, SNRPD1, DTYMK, PIGU, NME1, TXNL4A, IPO4, PES1, and
REXO4 was obtained. High expression of this signature indicates poor prognosis of HCC. PIGU was an independent prognostic factor of HCC, which was significantly associated with progression of HCC. Among them,
DTYMK and
NME1 enriched in pyrimidine metabolism,
SNRPD1 and
TXNL4A enriched in spliceosome and
PIGU enriched in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis pathways. High levels of
IPO4, NME1, PES1, PIGU and
SNRPD1 were closely associated with metastasis of HCC, and low levels of
IPO4, PIGU and
REOX4 were significantly associated with sorafenib resistance of HCC. High expression of the 9-gene signature was negatively correlated with the stromal cell infiltration, and positively correlated with specific immune subtypes-related to angiogenesis, M1/M2 macrophage polarization, and M2 response. The 9-gene signature was negatively correlated with the stroma, and
SNRPD1 and
TXNL4 were positively correlated with immune infiltrate.
NME1 was negatively correlated with tumor purity. Therefore, a 9-gene signature related to mRNAsi and poor prognosis in HCC were identified, which can be used as biomarkers for the diagnosis of HCC and functional mechanism exploration of CSCs in HCC. These genes such as
IPO4 and
PIGU might drive the transition of tumor cells into CSCs which possibly controls the balance between metastasis and drug resistance in HCC. The challenge on balance between metastasis and drug resistance for tumor therapy was firstly reported by the present study.
Keywords
Supplementary Material
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Cite This Article
YAO, X., LU, C., SHEN, J., JIANG, W., QIU, Y. et al. (2021). A novel nine gene signature integrates stemness characteristics associated with prognosis in hepatocellular carcinoma.
BIOCELL, 45(6), 1425–1448.