Saukkonen Kapo, Hagström Jaana, Mustonen Harri, Lehtinen Laura, Carpen Olli, Andersson Leif C, Seppänen Hanna, Haglund Caj
1 Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2 Translational Cancer Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
Tumour Biol. 2018 Mar;40(3):1010428318761494. doi: 10.1177/1010428318761494.
Expression of regenerating islet-derived protein 4 (REG4), a secretory protein involved in cell differentiation and proliferation, is upregulated in inflammatory bowel diseases and in many gastrointestinal malignancies. The prognostic significance of its expression in pancreatic ductal adenocarcinoma is unknown. Our aim was to investigate tumor tissue and serum REG4 expression in pancreatic ductal adenocarcinoma patients. We also evaluated as a control the diagnostic value of serum REG4 level in patients with chronic pancreatitis. Immunohistochemical expression of REG4 was evaluated in 154 surgical specimens and serum REG4 level in 130 samples from pancreatic ductal adenocarcinoma patients treated at Helsinki University Hospital, Finland, in 2000-2011. REG4 tissue and serum expression was assessed in relation to clinicopathological parameters and patient survival. A chronic pancreatitis control group comprised 34 patients who underwent pancreatic resection because of suspicion of malignancy. Significant survival differences were detectable in subgroups: in tumor stages IA-IIA, high serum REG4 level predicted worse survival (p=0.046). In patients with grade I tumor, positive tissue REG4 expression predicted better survival (p=0.006). In multivariate analysis, neither tissue nor serum REG4 expression was independent prognostic factors. Serum REG4 levels were higher in pancreatic ductal adenocarcinoma than in chronic pancreatitis (p=0.002), with diagnostic sensitivity of 45% and specificity of 91%. In logistic regression analysis, a multivariate model with REG4, CA19-9, and age provided sensitivity of 82% and specificity of 79%. REG4 tissue expression is a prognostic marker in subgroups of pancreatic ductal adenocarcinoma patients. Serum REG4 level might be useful in differential diagnosis between pancreatic ductal adenocarcinoma and chronic pancreatitis.
再生胰岛衍生蛋白4（REG4）是一种参与细胞分化和增殖的分泌蛋白，在炎症性肠病和许多胃肠道恶性肿瘤中表达上调。其在胰腺导管腺癌中表达的预后意义尚不清楚。我们的目的是研究胰腺导管腺癌患者的肿瘤组织和血清REG4表达情况。我们还评估了血清REG4水平在慢性胰腺炎患者中的诊断价值，作为对照。对2000年至2011年在芬兰赫尔辛基大学医院接受治疗的154例胰腺导管腺癌手术标本中的REG4进行免疫组化表达评估，并对130份样本中的血清REG4水平进行检测。评估REG4组织和血清表达与临床病理参数及患者生存情况的关系。慢性胰腺炎对照组包括34例因怀疑恶性肿瘤而接受胰腺切除术的患者。在亚组中可检测到显著的生存差异：在IA-IIA期肿瘤中，高血清REG4水平预示着较差的生存情况（p=0.046）。在I级肿瘤患者中，组织REG4阳性表达预示着较好的生存情况（p=0.006）。在多变量分析中，组织和血清REG4表达均不是独立的预后因素。胰腺导管腺癌患者的血清REG4水平高于慢性胰腺炎患者（p=0.002），诊断敏感性为45%，特异性为91%。在逻辑回归分析中，包含REG4、CA19-9和年龄的多变量模型的敏感性为82%，特异性为79%。REG4组织表达是胰腺导管腺癌患者亚组中的一个预后标志物。血清REG4水平可能有助于胰腺导管腺癌与慢性胰腺炎的鉴别诊断。
