Ormanns Steffen, Haas Michael, Remold Anna, Kruger Stephan, Holdenrieder Stefan, Kirchner Thomas, Heinemann Volker, Boeck Stefan
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany.
Int J Mol Sci. 2017 May 19;18(5):1094. doi: 10.3390/ijms18051094.
The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome. At chemotherapy initiation, 128 pts had metastatic PC; most pts ( = 99) received a gemcitabine-based regimen. SMAD4 loss was detected in 92 pts (64%); patient characteristics such as gender, age, tumor grading, disease stage or number of metastatic sites had no significant impact on tumoral SMAD4 status. In univariate analyses, SMAD4 loss had no impact on overall survival (hazard ratio (HR) 1.008, = 0.656); however, we observed a prolonged progression-free survival (HR 1.565, = 0.038) in pts with tumoral SMAD4 loss. This finding was confirmed in multivariate analyses (HR 1.790, = 0.040), but only for gemcitabine-treated pts. In contrast to previous studies in resectable PC, loss of SMAD4 expression was not associated with a negative outcome in patients with advanced PC receiving systemic chemotherapy.
肿瘤抑制因子抗果蝇dpp蛋白同源物4（SMAD4）在晚期胰腺癌（aPC）患者中的作用尚未明确。本转化研究旨在评估肿瘤SMAD4缺失对接受姑息化疗的胰腺癌患者临床病理参数和预后的影响。我们采用免疫组织化学方法，检测了143例在已完成的前瞻性临床和生物标志物试验中接受治疗的aPC患者肿瘤组织中SMAD4的表达。在单因素和多因素分析中，SMAD4表达状态与患者的临床病理特征及预后相关。化疗开始时，128例患者患有转移性胰腺癌；大多数患者（n = 99）接受了以吉西他滨为基础的治疗方案。92例患者（64%）检测到SMAD4缺失；患者的性别、年龄、肿瘤分级、疾病分期或转移部位数量等特征对肿瘤SMAD4状态无显著影响。在单因素分析中，SMAD4缺失对总生存期无影响（风险比（HR）1.008，P = 0.656）；然而，我们观察到肿瘤SMAD4缺失的患者无进展生存期延长（HR 1.565，P = 0.038）。这一发现在多因素分析中得到证实（HR 1.790，P = 0.040），但仅适用于接受吉西他滨治疗的患者。与之前关于可切除胰腺癌的研究不同，在接受全身化疗的晚期胰腺癌患者中，SMAD4表达缺失与不良预后无关。
