A poor prognosis in human hepatocellular carcinoma is associated with low expression of DPP4

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.

本研究旨在探讨二肽基肽酶4（DPP4）在肝细胞癌（HCC）中的预后作用。研究收集了327例HCC患者的福尔马林固定石蜡包埋组织标本，采用免疫组化分析检测DPP4的表达特征，并评估其在HCC组织中的预后价值，包括总生存期（OS）与复发时间。此外，本研究还通过患者来源异种移植瘤（PDX）模型，在体内水平探究DPP4表达与肿瘤生长的相关性。相较于配对癌旁组织，HCC组织中DPP4呈现低表达状态：59例标本中共38例出现表达下调，占比64.4%（P=0.0202）。DPP4表达与TNM分期（P=0.038）、肿瘤数目（P=0.035）及血管侵犯（P=0.024）显著相关；相较于TNM分期I期、单发肿瘤且无微血管侵犯的患者，TNM分期II~III-V期、多发肿瘤及存在微血管侵犯的患者，其DPP4表达水平显著降低。值得注意的是，DPP4低表达的HCC组织患者总生存期显著劣于DPP4高表达者（P=0.016）；PDX模型实验结果同样显示，DPP4低表达的HCC患者体内肿瘤生长速度显著快于DPP4高表达者。本研究结果表明，DPP4低表达可增强肝细胞癌的侵袭性，并提示不良预后。