Geng Xiaocong, Liu Yueyang, Diersch Sandra, Kotzsch Matthias, Grill Sabine, Weichert Wilko, Kiechle Marion, Magdolen Viktor, Dorn Julia
Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
Medizinisches Labor Ostsachsen, Dresden, Germany.
PLoS One. 2017 Nov 2;12(11):e0186847. doi: 10.1371/journal.pone.0186847. eCollection 2017.
KLK9, 10, 11, and 15 may represent potential cancer biomarkers for evaluating ovarian cancer prognosis. In the present study, we selected a homogeneous cohort including 139 patients of advanced high-grade serous ovarian cancer (FIGO stage III/IV) and assessed the mRNA levels of KLK9, 10, 11, and 15 in tumor tissue by quantitative PCR. No significant associations of KLK9, 10, 11, and 15 mRNA with established clinical parameters (residual tumor mass, ascitic fluid volume) were found. Pronounced correlations between KLK10/KLK11 (rs = 0.647) and between KLK9/KLK15 (rs = 0.716) mRNA, but not between other combinations, indicate coordinate expression of distinct pairs of peptidases. In univariate Cox regression analysis, elevated KLK11 mRNA levels were significantly linked with prolonged overall survival (OS; p = 0.021) and progression-free survival (PFS; p = 0.008). KLK15 mRNA levels showed a trend towards significance in case of OS (p = 0.06); KLK9 and KLK10 mRNA expression levels were not associated with patients' outcome. In multivariable Cox analysis, KLK11 mRNA expression levels, apart from residual tumor mass, remained an independent predictive marker for OS (p = 0.007) and PFS (p = 0.015). Here, elevated KLK15 mRNA expression levels turned out to be significantly related to prolonged OS (p = 0.025) as well. High KLK11 but not the other KLK mRNA levels can be considered as strong independent favorable prognostic factor in this major ovarian cancer subtype.
激肽释放酶9、10、11和15可能是评估卵巢癌预后的潜在癌症生物标志物。在本研究中,我们选取了一个同质队列,其中包括139例晚期高级别浆液性卵巢癌患者(国际妇产科联盟分期III/IV期),并通过定量PCR评估肿瘤组织中激肽释放酶9、10、11和15的mRNA水平。未发现激肽释放酶9、10、11和15的mRNA与既定临床参数(残留肿瘤肿块、腹水体积)之间存在显著关联。激肽释放酶10/激肽释放酶11(rs = 0.647)以及激肽释放酶9/激肽释放酶15(rs = 0.716)的mRNA之间存在显著相关性,但其他组合之间无相关性,这表明不同肽酶对之间存在协同表达。在单变量Cox回归分析中,激肽释放酶11的mRNA水平升高与总生存期(OS;p = 0.021)延长和无进展生存期(PFS;p = 0.008)显著相关。激肽释放酶15的mRNA水平在OS方面显示出显著趋势(p = 0.06);激肽释放酶9和激肽释放酶10的mRNA表达水平与患者预后无关。在多变量Cox分析中,除残留肿瘤肿块外,激肽释放酶11的mRNA表达水平仍然是OS(p = 0.007)和PFS(p = 0.015)的独立预测指标。在此,激肽释放酶15的mRNA表达水平升高也被证明与OS延长显著相关(p = 0.025)。在这种主要的卵巢癌亚型中,高激肽释放酶11而非其他激肽释放酶的mRNA水平可被视为强大的独立有利预后因素。