背景:肝癌(LIHC)是一种发生在肝脏中的恶性肿瘤,在癌症中具有很高的死亡率。ING家族基因被鉴定为肿瘤抑制基因。这些基因表达失调会导致细胞周期停滞,衰老和/或凋亡。ING家族基因是抗癌治疗的有希望的靶标。然而,他们在LIHC中的作用仍然没有得到很好的理解。
目的:为了更好地了解ING家族成员在LIHC中的重要作用。
方法:一系列生物信息学方法(包括基因表达分析,遗传改变分析,生存分析,免疫浸润分析,预测ING1的上游microRNAs(miRNAs)和长链非编码RNAs(lncRNAs),以及ING1相关基因功能富集分析)用于研究表达谱,临床关系,LIHC中ING的预后意义和免疫浸润。在LIHC中研究了ING家族基因表达与肿瘤相关免疫检查点之间的关系。初步探讨了ING1介导肝癌发生的分子机制。
结果:在不同数据库中分析了LIHC中不同ING家族基因的mRNA/蛋白表达,显示ING家族基因在LIHC中高表达。在366名LIHC患者的47个样本中,ING家族基因的改变率为13%。通过对表达式的综合分析,ING家族基因的临床病理参数和预后价值,确定了ING1/5。ING1/5与LIHC预后不良有关,提示它们可能在LIHC肿瘤发生和进展中起关键作用。ING1的靶miRNA之一被鉴定为hsa-miR-214-3p。hsa-miR-214-3p的两个上游lncRNAs,鉴定了U11328.1和HCG17。同时,我们发现ING家族基因的表达与免疫细胞浸润和免疫检查点基因相关。
结论:本研究为进一步研究ING家族基因在LIHC治疗和预后中的潜在机制和临床价值奠定了基础。
BACKGROUND: Liver cancer (LIHC) is a malignant tumor that occurs in the liver and has a high mortality in cancer. The ING family genes were identified as tumor suppressor genes. Dysregulated expression of these genes can lead to cell cycle arrest, senescence and/or apoptosis. ING family genes are promising targets for anticancer therapy. However, their role in LIHC is still not well understood.
OBJECTIVE: To have a better understanding of the important roles of ING family members in LIHC.
METHODS: A series of bioinformatics approaches (including gene expression analysis, genetic alteration analysis, survival analysis, immune infiltration analysis, prediction of upstream microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) of ING1, and ING1-related gene functional enrichment analysis) was applied to study the expression profile, clinical relationship, prognostic significance and immune infiltration of ING in LIHC. The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC. The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.
RESULTS: mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases, showing that ING family genes were highly expressed in LIHC. In 47 samples from 366 LIHC patients, the ING family genes were altered at a rate of 13%. By comprehensively analyzing the expression, clinical pathological parameters and prognostic value of ING family genes, ING1/5 was identified. ING1/5 was related to poor prognosis of LIHC, suggesting that they may play key roles in LIHC tumorigenesis and progression. One of the target miRNAs of ING1 was identified as hsa-miR-214-3p. Two upstream lncRNAs of hsa-miR-214-3p, U91328.1, and HCG17, were identified. At the same time, we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.
CONCLUSIONS: This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.