Niedworok Christian, Tschirdewahn Stephan, Reis Henning, Lehmann Nils, Szücs Miklós, Nyirády Péter, Romics Imre, Rübben Herbert, Szarvas Tibor
Department of Urology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Pathol Oncol Res. 2017 Jul;23(3):643-650. doi: 10.1007/s12253-016-0171-5. Epub 2016 Dec 23.
Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p < 0.001 and; 41 vs. 22 ng/ml; p = 0.002 respectively). In accordance, high CGA levels were correlated with poor DSS. In clinically localized cases, CGA levels alone were not prognostic, but its dichotomized combinations with PSA or MMP7 were independently associated with DSS (HR: 4.88, 95% CI: 1.35-17.71, p = 0.016, HR: 7.46, 1.65-33.63, p = 0.009, respectively). Elevated serum CGA levels in progressed PCA and its prognostic value suggest a potential for CGA in disease monitoring. Our results revealed no independent prognostic value for CGA as a single serum marker in clinically localized cases. However, when combining with PSA or MMP7, CGA may improve both marker's performance in distinguishing between clinically significant and indolent PCAs.
临床局限性前列腺癌（PCA）的更好预后预测迫在眉睫。以往使用不同研究终点的研究对于血清嗜铬粒蛋白A（CGA）在临床局限性PCA中的预后价值给出了相互矛盾的结果。然而，血清CGA尚未被检测与长期疾病特异性生存（DSS）这一最重要的研究终点之间的相关性。通过BRAHMS KRYPTOR在两个独立患者组中对127份血清样本和110份血浆样本检测了CGA和基质金属蛋白酶-7（MMP7）水平。CGA和MMP7浓度与临床病理及生存数据相关。此外，我们检测了CGA与前列腺特异性抗原（PSA）以及与当前已确定的预后因素MMP7的组合的预后价值。与临床局限性病例相比，血清和血浆样本中晚期病例的CGA浓度均显著升高（分别为45 vs. 23 ng/ml，p < 0.001；41 vs. 22 ng/ml，p = 0.002）。相应地，高CGA水平与不良DSS相关。在临床局限性病例中，单独的CGA水平并无预后价值，但其与PSA或MMP7的二分组合与DSS独立相关（风险比：4.88，95%置信区间：1.35 - 17.71，p = 0.016；风险比：7.46，1.65 - 33.63，p = 0.009）。进展期PCA中血清CGA水平升高及其预后价值提示CGA在疾病监测方面具有潜力。我们的结果显示，在临床局限性病例中，CGA作为单一血清标志物无独立预后价值。然而，当与PSA或MMP7联合时，CGA可能会提高这两种标志物区分临床显著性和惰性PCA的性能。
