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Abstract：
To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
ScRNA-seq was performed on two tumors collected from patients with AFPGC. InferCNV and sub-clustering were applied to identify typical AFPGC cells, followed by AddModuleScore, pathway enrichment, Pseudo-time, and Scenic analyses. Data from a gastric cancer (GC) cohort were collected for conjoint analysis. The analytical results were verified by cell experiments and immunohistochemistry.
AFPGC cells are similar to hepatocytes in transcriptome and transcriptional regulation, with kinetic malignancy-related pathways, compared to the common malignant epithelium. In addition, compared to common GC cells, malignancy-related pathways, such as epithelial-mesenchymal transition (EMT) and angiogenesis, were upregulated in AFPGC. Mechanistically, Dickkopf-1 (DKK1) was found to be associated with AFP expression and malignant phenotype upon combining our scRNA-seq data with a public database, which was further verified by a series of in vitro experiments and immunohistochemistry.
We demonstrated the single-cell characteristics of AFPGC and that DKK1 facilitates AFP expression and malignancy.
ScRNA-seq was performed on two tumors collected from patients with AFPGC. InferCNV and sub-clustering were applied to identify typical AFPGC cells, followed by AddModuleScore, pathway enrichment, Pseudo-time, and Scenic analyses. Data from a gastric cancer (GC) cohort were collected for conjoint analysis. The analytical results were verified by cell experiments and immunohistochemistry.
AFPGC cells are similar to hepatocytes in transcriptome and transcriptional regulation, with kinetic malignancy-related pathways, compared to the common malignant epithelium. In addition, compared to common GC cells, malignancy-related pathways, such as epithelial-mesenchymal transition (EMT) and angiogenesis, were upregulated in AFPGC. Mechanistically, Dickkopf-1 (DKK1) was found to be associated with AFP expression and malignant phenotype upon combining our scRNA-seq data with a public database, which was further verified by a series of in vitro experiments and immunohistochemistry.
We demonstrated the single-cell characteristics of AFPGC and that DKK1 facilitates AFP expression and malignancy.
摘要：
目的：在单细胞水平上表征甲胎蛋白（AFP）产生的胃癌（AFPGC），并鉴定AFP表达和恶性肿瘤的调节因子。
方法：对从AFPGC患者收集的两个肿瘤进行ScRNA-seq。InferCNV和亚聚类用于鉴定典型的AFPGC细胞，其次是AddModuleScore，途径富集，伪时间,和风景分析。收集来自胃癌（GC）队列的数据进行联合分析。通过细胞实验和免疫组织化学验证分析结果。
结果：AFPGC细胞在转录组和转录调节方面与肝细胞相似，与动力性恶性肿瘤相关的途径，与常见的恶性上皮相比。此外,与常见的GC细胞相比，恶性肿瘤相关途径，如上皮间质转化（EMT）和血管生成，在AFPGC中上调。机械上,在将我们的scRNA-seq数据与公共数据库相结合后，发现Dickkopf-1（DKK1）与AFP表达和恶性表型相关。经一系列体外实验和免疫组织化学进一步验证。
结论：我们证明了AFPGC的单细胞特征，DKK1促进AFP表达和恶性。
方法：对从AFPGC患者收集的两个肿瘤进行ScRNA-seq。InferCNV和亚聚类用于鉴定典型的AFPGC细胞，其次是AddModuleScore，途径富集，伪时间,和风景分析。收集来自胃癌（GC）队列的数据进行联合分析。通过细胞实验和免疫组织化学验证分析结果。
结果：AFPGC细胞在转录组和转录调节方面与肝细胞相似，与动力性恶性肿瘤相关的途径，与常见的恶性上皮相比。此外,与常见的GC细胞相比，恶性肿瘤相关途径，如上皮间质转化（EMT）和血管生成，在AFPGC中上调。机械上,在将我们的scRNA-seq数据与公共数据库相结合后，发现Dickkopf-1（DKK1）与AFP表达和恶性表型相关。经一系列体外实验和免疫组织化学进一步验证。
结论：我们证明了AFPGC的单细胞特征，DKK1促进AFP表达和恶性。
