目的·通过肿瘤转录组学筛选，明确在胰腺癌中因脂肪酸代谢紊乱引起上调的关键基因，并探究其中的锌指蛋白143（zinc finger protein 143，ZNF143）在胰腺癌中的表达及其对胰腺癌细胞迁移、侵袭能力的影响。方法·运用R语言整合Gene Expression Omnibus（GEO）数据库中GSE164760数据集、癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中179例胰腺癌组织和4例癌旁组织及GTEx（Genotype-Tissue Expression）数据库中167例胰腺正常组织的转录组数据；筛选分析胰腺癌中脂肪酸紊乱可能会诱导表达的潜在差异基因；qRT-PCR检测使用棕榈酸（palmitic acid，PA）或油酸（oleic acid，OA）处理24 h后胰腺癌细胞中筛选基因的mRNA水平变化。按照筛选基因ZNF143表达水平的中位数，将TCGA数据库中胰腺癌患者分为高低表达2组，并将2组分析所得的差异基因进行京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路和基因本体论（Gene Ontology，GO）富集分析；通过细胞划痕实验、侵袭实验检测使用siRNA敲低ZNF143对胰腺癌细胞的迁移、侵袭能力的影响；使用蛋白质印迹法（Western blotting）检测敲低ZNF143对上皮-间质转化（epithelial-mesenchymal transition，EMT）相关蛋白及Wnt/β-catenin通路的影响。结果·分析了胰腺癌和肝癌中脂质代谢紊乱上调的关键基因，其中ZNF143是胰腺癌脂肪酸蓄积诱导的潜在基因之一；体外实验验证棕榈酸或油酸处理胰腺癌细胞后，ZNF143的mRNA水平均明显上调；KEGG和GO富集分析均显示ZNF143相关差异基因主要富集于细胞黏附相关通路；功能实验表明，转染ZNF143 siRNA的胰腺癌细胞迁移与侵袭能力均被下调，且EMT相关蛋白的表达也降低，可能与Wnt/β-catenin通路激活有关。结论·脂肪酸蓄积上调ZNF143在胰腺癌细胞中的mRNA表达含量，且ZNF143可能通过激活Wnt/β-catenin通路介导EMT，进而增强胰腺癌细胞的迁移和侵袭能力。

Objective ·To identify key genes that may be regulated by fatty acid alteration in pancreatic cancer through tumor transcriptome screening, and to explore the expression of zinc finger protein 143 (ZNF143) in pancreatic cancer and its effect on the migration and invasion of pancreatic cancer cells. Methods ·The R language was utilized to integrate transcriptome data, including the GSE164760 dataset from the Gene Expression Omnibus (GEO) database, 179 pancreatic cancer tissue samples and 4 adjacent non-cancerous tissue samples from The Cancer Genome Atlas (TCGA) database, as well as 167 normal pancreatic tissue samples from the Genotype-Tissue Expression (GTEx) database. We conducted screening and analysis of potential differential genes that may be induced by dysregulation of fatty acid metabolism in pancreatic cancer. After treating pancreatic cancer cells with palmitic acid (PA) and oleic acid (OA) for 24 hours, the mRNA levels of candidate genes were detected by qRT-PCR. According to the median expression level of the screened gene, pancreatic cancer patients in the TCGA database were divided into two groups with high and low expression of ZNF143. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed for the differential genes of the two groups. siRNA was used to knock down the expression of ZNF143 in pancreatic cancer cells, and the effects on cell migration and invasion were examined by wound healing assay and invasion assay. Western blotting was used to explore the impact of ZNF143 on epithelial mesenchymal transition (EMT)-related proteins and the Wnt/β-catenin pathway. Results ·The bioinformatics database was processed to analyze key genes associated with the up-regulation of genes in lipid metabolism disorders in pancreatic cancer and liver cancer. Among them, ZNF143 was a potential gene associated with fatty acid accumulation in pancreatic cancer. In vitro experiments confirmed that the mRNA level of ZNF143 was significantly up-regulated after treating pancreatic cancer cells with palmitic acid or oleic acid. Both KEGG and GO enrichment analyses demonstrated that the differentially expressed genes associated with ZNF143 were predominantly enriched in adhesion pathways. In functional experiments, the migration and invasion abilities of pancreatic cancer cells transfected with ZNF143 siRNA were reduced, and the expression of EMT-related proteins was also decreased, potentially related to the activation of the Wnt/β- catenin pathway. Conclusion ·Fatty acid accumulation up-regulates the mRNA expression of ZNF143 in pancreatic cancer cells, and ZNF143 may enhance the migration and invasion of these cells by facilitating EMT through activation of the Wnt/β-catenin pathway.