Growth Differentiation Factor 1-Induced Tumour Plasticity Provides A Therapeutic Window for Immunotherapy in Hepatocellular Carcinoma. Growth Differentiation Factor 1-Induced Tumour Plasticity Provides A Therapeutic Window for Immunotherapy in Hepatocellular Carcinoma

Poorly differentiated hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis. Here the authors show that GDF1, a member of the TGF-β superfamily, is highly expressed in high-grade poorly differentiated HCC and is associated with tumor plasticity, and that GDF1-induced re-expression of cancer testis antigens could render tumors sensitive to immune checkpoint inhibition. Overall design: RNA sequencing was performed in PLC-8024-CTR and PLC-8024-GDF1 cells at Shanghai Shenggong Biotech Co., Ltd. RNA samples were analyzed by RNA sequencing based on the manufacturer’s protocols. Briefly, Illumina HiSeq platform was used to sequence the RNA samples for the subsequent generation of raw data. R package was utilized to select genes with significantly differential expression. In order to obtain the significant differential genes, the screening conditions were set as follows: q-value 1. GSEA enrichment analysis were used for functional pathway analysis.

低分化肝细胞癌（hepatocellular carcinoma, HCC）是一类侵袭性强、预后极差的疾病。本研究显示，转化生长因子-β（TGF-β）超家族成员生长分化因子1（GDF1）在高级别低分化HCC中高表达，且与肿瘤可塑性密切相关；GDF1诱导的癌睾抗原（cancer testis antigens）重表达，可使肿瘤对免疫检查点抑制（immune checkpoint inhibition）治疗产生敏感性。
实验设计概况：
本研究于上海生工生物科技有限公司对PLC-8024-CTR与PLC-8024-GDF1细胞开展RNA测序（RNA sequencing）实验。RNA样本的测序分析严格遵循试剂盒制造商的操作规程进行。简言之，本研究采用Illumina HiSeq测序平台（Illumina HiSeq platform）对RNA样本进行测序，以获取原始测序数据。使用R软件包（R package）筛选显著差异表达基因。为获取显著差异表达基因，本研究设置的筛选条件如下：q值为1。采用基因集富集分析（Gene Set Enrichment Analysis, GSEA）进行功能通路分析。