Open Access

ARTICLE

A novel nine gene signature integrates stemness characteristics associated with prognosis in hepatocellular carcinoma

XINGHONG YAO^1,2,#, CHENGQUAN LU^3,#, JUNYI SHEN¹, WENLI JIANG¹, YAN QIU¹, YE ZENG^1,*, LIANG LI^1,*

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:
# Authors contributed equally

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.

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Supplementary Material

Supplementary Material File

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