Gene profiling of human adult and pediatric liver cancer cells

In an effort to comprehend some of the molecular differences between two cancers that originate in the same tissue, adult HCC and pediatric HB, we profiled four HCC and four HB cell lines using RNA sequencing. We identified an enhanced sugar uptake and usage in HB tumors compared to adult HCC, and two different metabolic subtypes of HB. We identified an enhanced sugar uptake and usage in HB tumors compared to adult HCC, and two different metabolic subtypes of HB. In particular, we showed that embryonal HB cell lines largely rely on glycolysis and express higher level of GLUT3, together with HK1, PFKP and LDHB coding for enzyme of glycolysis. On the contrary, fetal tumors express genes involved in gluconeogenesis, and as notable exception they express HK2, which is often over-expressed in adult solid tumors. Importantly, we found that the different utilization of HK isoforms renders the two HB subtypes sensitive to specific glycolysis inhibitors. Overall design: HCC and HB gene profiles were generated by deep sequencing, in duplicates, using Illumina HiSeq 2500.

为探究起源于同一组织的两种癌症——成人肝细胞癌（hepatocellular carcinoma, HCC）与儿童肝母细胞瘤（hepatoblastoma, HB）——之间的分子差异，本研究通过RNA测序（RNA sequencing）对4株HCC细胞系及4株HB细胞系开展转录组表征分析。研究发现，相较于成人HCC，HB肿瘤的葡萄糖摄取与代谢活性显著增强，且HB存在两种不同的代谢亚型。研究发现，相较于成人HCC，HB肿瘤的葡萄糖摄取与代谢活性显著增强，且HB存在两种不同的代谢亚型。具体而言，本研究证实，胚胎型HB细胞系主要依赖糖酵解供能，且高表达葡萄糖转运蛋白3（GLUT3），同时高表达编码糖酵解关键酶的己糖激酶1（HK1）、磷酸果糖激酶P（PFKP）及乳酸脱氢酶B（LDHB）。与之相反，胎儿型HB肿瘤则表达糖异生相关基因；值得注意的是，胎儿型HB肿瘤高表达己糖激酶2（HK2）——该基因在成人实体瘤中通常呈高表达状态。尤为重要的是，本研究发现，两种HB亚型对己糖激酶同工酶的差异化利用，使其对特定糖酵解抑制剂具有敏感性。实验整体设计：本研究采用Illumina HiSeq 2500测序平台，通过双重复实验开展深度测序，以获取HCC与HB的基因表达谱。