Wu Meng-Yao, Shen Meng, Xu Meng-Dan, Yu Zheng-Yuan, Tao Min
Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, China.
Gland Surg. 2020 Dec;9(6):2125-2135. doi: 10.21037/gs-20-828.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide due to its ineffective diagnosis and poor prognosis. The longest median overall survival (OS) to PDAC patients has been provided by FOLFIRINOX. It is essential to identify the mechanisms of FOLFIRINOX to gain new insights for the treatment of PDAC.
We compared gene expression levels of PDAC patients who received neoadjuvant FOLFIRINOX prior to surgery with those of patients who received no neoadjuvant chemotherapy. Bioinformatics analysis was applied to screen differentially expressed genes (DEGs). Three microarray data sets were downloaded to analyze gene expression data between PDAC and adjacent non-tumor tissues. Overlapping DEGs were subjected to Kaplan-Meier survival analysis. The genes relating to poor outcomes and would be decreased after FOLFIRINOX were input into the Oncomine, University of Alabama Cancer (UALCAN), and LinkedOmics databases to analyze the gene expression and regulation networks.
A total of 83 differentially expressed genes (DEGs) were screened and subjected to bioinformatics analysis, which indicated FOLFIRINOX influenced the immune microenvironment of PDAC. Seventy-three genes significantly associated with the OS of PDAC patients. A Venn diagram revealed CXCL5 and PLAU were related to poor outcomes and would decrease after FOLFIRINOX chemotherapy of PDAC patients. It turned out that CXCL5 participated in the immune response-regulating signaling pathway in PDAC patients.
FOLFIRINOX regulated tumor immunity by reducing expression of the immunosuppressive gene CXCL5, laying a foundation for further study of combination therapy of FOLFIRINOX and immunotherapy.
胰腺导管腺癌（PDAC）是全球最致命的恶性肿瘤之一，因其诊断效果不佳且预后不良。FOLFIRINOX方案为PDAC患者提供了最长的中位总生存期（OS）。确定FOLFIRINOX方案的作用机制对于获得PDAC治疗的新见解至关重要。
我们比较了术前接受新辅助FOLFIRINOX方案的PDAC患者与未接受新辅助化疗的患者的基因表达水平。应用生物信息学分析筛选差异表达基因（DEG）。下载三个微阵列数据集以分析PDAC与相邻非肿瘤组织之间的基因表达数据。对重叠的DEG进行Kaplan-Meier生存分析。将与预后不良且在FOLFIRINOX方案后会降低的基因输入Oncomine、阿拉巴马大学癌症（UALCAN）和LinkedOmics数据库，以分析基因表达和调控网络。
共筛选出83个差异表达基因（DEG）并进行生物信息学分析，结果表明FOLFIRINOX方案影响了PDAC的免疫微环境。73个基因与PDAC患者的OS显著相关。维恩图显示CXCL5和PLAU与预后不良相关，且在PDAC患者接受FOLFIRINOX化疗后会降低。结果表明CXCL5参与了PDAC患者的免疫反应调节信号通路。
FOLFIRINOX方案通过降低免疫抑制基因CXCL5的表达来调节肿瘤免疫，为进一步研究FOLFIRINOX方案与免疫治疗的联合治疗奠定了基础。
