@Article{biocell.2021.017289,
AUTHOR = {XINGHONG YAO, CHENGQUAN LU, JUNYI SHEN, WENLI JIANG, YAN QIU, YE ZENG, LIANG LI},
TITLE = {A novel nine gene signature integrates stemness characteristics associated with prognosis in hepatocellular carcinoma},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {6},
PAGES = {1425--1448},
URL = {http://www.techscience.com/biocell/v45n6/44263},
ISSN = {1667-5746},
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 <i>PSMG3, SNRPD1, DTYMK, PIGU, NME1, TXNL4A, IPO4, PES1</i>, and <i>REXO4</i> 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, <i>DTYMK</i> and <i>NME1</i> enriched in pyrimidine metabolism, <i>SNRPD1</i> and <i>TXNL4A</i> enriched in spliceosome and <i>PIGU</i> enriched in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis pathways. High levels of <i>IPO4, NME1, PES1, PIGU</i> and <i>SNRPD1</i> were closely associated with metastasis of HCC, and low levels of <i>IPO4, PIGU</i> and <i>REOX4</i> 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 <i>SNRPD1</i> and <i>TXNL4</i> were positively correlated with immune infiltrate. <i>NME1</i> 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 <i>IPO4</i> and <i>PIGU</i> 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.},
DOI = {10.32604/biocell.2021.017289}
}