Zhong Xiaodan, Zhang Songling, Zhang Yutong, Jiang Zongmiao, Li Yanan, Chang Jian, Niu Junqi, Shi Ying
Department of Pediatric Oncology, The First Hospital of Jilin University, Changchun, China.
Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2021 Dec 20;9:769547. doi: 10.3389/fcell.2021.769547. eCollection 2021.
Neuroblastoma (NB) is the most common solid tumor apart from central nervous system malignancies in children aged 0-14 years, and the outcomes of high-risk patients are dismal. High mobility group box 3 (HMGB3) plays an oncogenic role in many cancers; however, its biological role in NB is still unclear. Using data mining, we found that HMGB3 expression was markedly elevated in NB patients with unfavorable prognoses. When HMGB3 expression in NB cell lines was inhibited, cell proliferation, migration, and invasion were suppressed, and HMGB3 knockdown inhibited NB tumor development in mice. RT-PCR was employed to detect mRNA expression of nine coexpressed genes in response to HMGB3 knockdown, and TPX2 was identified. Furthermore, overexpression of TPX2 reversed the cell proliferation effect of HMGB3 silencing. Multivariate Cox regression analysis indicated that HMGB3 and TPX2 might be independent prognostic factors for overall survival and event-free survival, which showed the highest significance ( < 0.001). According to the nomogram predictor constructed, the integration of gene expression and clinicopathological features exhibited better prognostic prediction power. Furthermore, the random forest algorithm and receiver operating characteristic curves also showed that HMGB3 and TPX2 played important roles in discriminating the vital status (alive/dead) of patients in the NB datasets. Our informatics analysis and biological experiments suggested that HMGB3 is correlated with the unfavorable clinical outcomes of NB, and plays an important role in promoting cell growth, proliferation, and invasion in NB, potentially representing a new therapeutic target for tumor progression.
神经母细胞瘤（NB）是0 - 14岁儿童中除中枢神经系统恶性肿瘤外最常见的实体瘤，高危患者的预后很差。高迁移率族蛋白B3（HMGB3）在许多癌症中发挥致癌作用；然而，其在NB中的生物学作用仍不清楚。通过数据挖掘，我们发现HMGB3表达在预后不良的NB患者中显著升高。当NB细胞系中的HMGB3表达受到抑制时，细胞增殖、迁移和侵袭受到抑制，并且HMGB3基因敲低抑制了小鼠体内NB肿瘤的发展。采用RT-PCR检测9个共表达基因在HMGB3基因敲低后的mRNA表达，并鉴定出TPX2。此外，TPX2的过表达逆转了HMGB3沉默对细胞增殖的影响。多因素Cox回归分析表明，HMGB3和TPX2可能是总生存和无事件生存的独立预后因素，具有最高的显著性（<0.001）。根据构建的列线图预测模型，基因表达与临床病理特征的整合表现出更好的预后预测能力。此外，随机森林算法和受试者工作特征曲线也表明，HMGB3和TPX2在区分NB数据集中患者的生存状态（存活/死亡）方面发挥重要作用。我们的信息学分析和生物学实验表明，HMGB3与NB不良临床结局相关，在促进NB细胞生长、增殖和侵袭中起重要作用，可能是肿瘤进展的一个新治疗靶点。
