Ormanns Steffen, Haas Michael, Baechmann Sibylle, Altendorf-Hofmann Annelore, Remold Anna, Quietzsch Detlef, Clemens Michael R, Bentz Martin, Geissler Michael, Lambertz Helmut, Kruger Stephan, Kirchner Thomas, Heinemann Volker, Boeck Stefan
Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Strasse 36, D-80337 Munich, Germany.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistrasse 15, D-81377 Munich, Germany.
Br J Cancer. 2016 Dec 6;115(12):1520-1529. doi: 10.1038/bjc.2016.355. Epub 2016 Nov 1.
Conflicting results on the role of secreted protein acidic and rich in cysteins (SPARC) expression have been reported in resected pancreatic ductal adenocarcinoma (PDAC), and its prognostic and/or predictive role in advanced PDAC (aPDAC) has not been extensively investigated yet. This study was designed to evaluate SPARC expression as a biomarker in aPDAC patients (pts) not receiving nab-paclitaxel.
Using immunohistochemistry, we examined the stromal as well as the tumoral (i.e., cytoplasmic) SPARC expression in tumour tissue (primary tumours and metastases) of 134 aPDAC pts participating in completed prospective clinical and biomarker trials. The SPARC expression levels were correlated to the pts' clinicopathological parameters and survival times.
Sixty-seven per cent of the analysed tumours showed high stromal SPARC expression, which was not associated with overall survival (OS, median 9.1 vs 7.6 months, P=0.316). A positive cytoplasmic SPARC expression was detected in 55% of the tumours and correlated significantly with inferior progression-free survival (PFS, 6.2 vs 8.6 months, P=0.004) and OS (7.8 vs 8.4 months, P=0.032). This association was strongest for pts, where primary tumour tissue was examined (PFS: 6.7 vs 10.8 months, P=0.004; OS: 7.9 vs 11.9 months, P=0.030), whereas no significant correlation was detected for pts, where only metastatic tissue was available (PFS: 5.8 vs 6.6 months, P=0.502; OS: 7.0 vs 7.8 months, P=0.452). In pts receiving gemcitabine-based chemotherapy cytoplasmic SPARC expression was significantly associated with an inferior PFS and OS (PFS: 6.2 vs 9.2 months, P=0.002; OS 7.3 vs 9.9 months, P=0.012), whereas no such association was detected for stromal SPARC expression or for pts receiving fluoropyrimidine-based chemotherapy.
We identified cytoplasmic SPARC expression in the primary tumour as a biomarker associated with inferior PFS and OS in aPDAC. Cytoplasmic SPARC expression may furthermore act as a negative predictive biomarker in pts treated with gemcitabine-based chemotherapy.
关于富含半胱氨酸的酸性分泌蛋白（SPARC）表达在切除的胰腺导管腺癌（PDAC）中的作用，已有相互矛盾的结果报道，而其在晚期PDAC（aPDAC）中的预后和/或预测作用尚未得到广泛研究。本研究旨在评估SPARC表达作为未接受白蛋白结合型紫杉醇的aPDAC患者（pts）生物标志物的情况。
我们采用免疫组织化学方法，检测了134例参与已完成的前瞻性临床和生物标志物试验的aPDAC患者肿瘤组织（原发肿瘤和转移灶）中基质以及肿瘤（即细胞质）SPARC的表达。SPARC表达水平与患者的临床病理参数和生存时间相关。
67%的分析肿瘤显示基质SPARC高表达，这与总生存期（OS，中位生存期9.1个月对7.6个月，P = 0.316）无关。55%的肿瘤检测到细胞质SPARC阳性表达，且与较差的无进展生存期（PFS，6.2个月对8.6个月，P = 0.004）和OS（7.8个月对8.4个月，P = 0.032）显著相关。这种关联在检测原发肿瘤组织的患者中最为明显（PFS：6.7个月对10.8个月，P = 0.004；OS：7.9个月对11.9个月，P = 0.030），而在仅获得转移组织的患者中未检测到显著相关性（PFS：5.8个月对6.6个月，P = 0.502；OS：7.0个月对7.8个月，P = 0.452）。在接受吉西他滨为基础的化疗患者中，细胞质SPARC表达与较差的PFS和OS显著相关（PFS：6.2个月对9.2个月，P = 0.002；OS 7.3个月对9.9个月，P = 0.012），而基质SPARC表达或接受氟嘧啶为基础化疗的患者未检测到这种关联。
我们确定原发肿瘤中的细胞质SPARC表达是aPDAC中与较差PFS和OS相关的生物标志物。细胞质SPARC表达还可能作为接受吉西他滨为基础化疗患者的阴性预测生物标志物。
