Differential Gene Expression Profiles of Pancreatic Ductal Adenocarcinomas Among African American and Caucasian American Patients

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. In the United States (US), African Americans (AA) have higher PDAC incidence and mortality than Caucasian Americans (CA). This study aimed to identify distinct gene expression patterns and differentially regulated pathways in AA and CA PDACs. METHODS: Whole transcriptomic analyses were conducted on FFPE sections of PDACs (n=40) from AA (9 PDAC/3 normal) and CA (31 PDAC/5 normal) tissues to evaluate differential expression and signaling pathways within and between racial groups and to identify distinctive and common genes/pathways. RESULTS: We identified uniquely upregulated genes in both racial groups. Among the 25 top upregulated genes in AA PDACs, compared to their normal tissues, were CHST15, PARP15, and NUDT16. Altered pathways in AA PDACs included glycerophospholipid metabolism and regulation of lipolysis in adipocytes. In contrast, a different set of top 25 upregulated genes was found in CA PDACs, including SERPINB3, PADI1, H3C8, and ZNF488. The altered pathways in CA PDACs included cellular senescence and PD-L1/PD-1 checkpoint pathways. Thirteen genes (seven upregulated and six downregulated) were differentially modulated in AA vs. CA PDACs. Using a publicly available database, we analyzed the top 25 upregulated genes (normal vs. tumor) and seven differentially upregulated genes (AA vs. CA) for associations with survival outcomes. Eight genes (CHST15, PARP15, NUDT16, SERPINB3, PADI1, H3C8, ZNF488, and LETM2) correlated with poor survival. CONCLUSION: These findings show distinct gene expression profiles and modulated pathways in AA and CA PDACs, supporting development of race-based therapeutic targets. Overall design: Whole transcriptomic analyses were conducted on FFPE sections of PDACs (n=40) from AA (9 PDAC/3 normal) and CA (31 PDAC/5 normal) tissues to evaluate differential expression and signaling pathways within and between racial groups and to identify distinctive and common genes/pathways.

## 研究目的
胰腺导管腺癌（Pancreatic ductal adenocarcinoma, PDAC）是第三大癌症相关死亡病因。在美国，非裔美国人（African Americans, AA）的PDAC发病率与死亡率均高于白人美国人（Caucasian American, CA）。本研究旨在明确非裔美国人与白人美国人PDAC患者中独特的基因表达模式及差异调控通路。
## 研究方法
本研究对来自非裔美国人（9例PDAC组织/3例正常组织）与白人美国人（31例PDAC组织/5例正常组织）的40份福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）PDAC组织切片开展全转录组分析，以评估种族组内及组间的差异表达与信号通路，并识别特异性及共通的基因/通路。
## 研究结果
本研究在两个种族组中均鉴定出了独有的上调基因。相较于正常组织，非裔美国人PDAC患者的前25个上调基因包括CHST15、PARP15与NUDT16。非裔美国人PDAC患者的异常通路包括甘油磷脂代谢及脂肪细胞脂解调控。与之相反，白人美国人PDAC患者的前25个上调基因则为另一组，包括SERPINB3、PADI1、H3C8及ZNF488。白人美国人PDAC患者的异常通路包括细胞衰老及PD-L1/PD-1检查点通路。相较于白人美国人PDAC，非裔美国人PDAC中有13个基因（7个上调、6个下调）存在差异调控。通过公共数据库，本研究分析了前25个上调基因（正常组织vs肿瘤组织）及7个差异上调基因（非裔美国人vs白人美国人）与生存结局的相关性。其中8个基因（CHST15、PARP15、NUDT16、SERPINB3、PADI1、H3C8、ZNF488及LETM2）与不良生存相关。
## 研究结论
本研究结果显示，非裔美国人与白人美国人PDAC患者存在独特的基因表达谱与调控通路，为基于种族的治疗靶点开发提供了依据。
## 整体实验设计
本研究对来自非裔美国人（9例PDAC组织/3例正常组织）与白人美国人（31例PDAC组织/5例正常组织）的40份福尔马林固定石蜡包埋PDAC组织切片开展全转录组分析，以评估种族组内及组间的差异表达与信号通路，并识别特异性及共通的基因/通路。