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在人类肝细胞癌中,预后不良与 DPP4 表达水平低有关。

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

机构信息

Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing College, Jiaxing, Zhejiang, China.

出版信息

Braz J Med Biol Res. 2020 Apr 9;53(4):e9114. doi: 10.1590/1414-431X20209114. eCollection 2020.

Abstract

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.

摘要

本研究旨在探讨二肽基肽酶 4(DPP4)表达在肝细胞癌(HCC)中的预后作用。收集了 327 例 HCC 患者的福尔马林固定石蜡包埋标本,测量 DPP4 表达。利用免疫组织化学分析检测 DDP4 在 HCC 组织中的表达特征和预后价值(总生存期(OS)和复发时间)。此外,还使用患者衍生的异种移植(PDX)模型评估 DPP4 表达与体内肿瘤生长之间的相关性。与配对的肿瘤周围组织相比,DPP4 在 HCC 组织中低表达(59 例中有 38 例下调,64.4%,P=0.0202)。DPP4 表达与 TNM 分期(P=0.038)、肿瘤数量(P=0.035)和血管侵犯(P=0.024)显著相关,与 TNM 分期 II 和 III-V 期、多发肿瘤和微血管侵犯的患者相比,DPP4 表达明显减少,而与 TNM 分期 I 期、单发肿瘤和无微血管侵犯的患者相比。值得注意的是,与 DPP4 高表达的 HCC 组织相比,DPP4 低表达的 HCC 组织的 OS 较差(P=0.016),PDX 模型的结果表明,与 DPP4 高表达的 HCC 患者相比,DPP4 低表达的 HCC 患者的肿瘤生长速度明显更快。我们的研究结果表明,DPP4 水平低可能影响 HCC 的侵袭性,并导致预后不良。

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