Urinary kallikrein 10 predicts the incurability of gastric cancer.
Urinary kallikrein 10 predicts the incurability of gastric cancer.
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DOI：
10.18632/oncotarget.16453
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发表时间：
2017-04-25
期刊：
影响因子：
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通讯作者：
Joh T
中科院分区：
文献类型：
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作者：
Shimura T;Ebi M;Yamada T;Yamada T;Katano T;Nojiri Y;Iwasaki H;Nomura S;Hayashi N;Mori Y;Kataoka H;Moses MA;Joh T
目前的成像方式不足以识别不可手术的肿瘤因素，包括远处转移和局部浸润。因此，我们进行了这项研究，使用尿液样本发现非侵入性生物标志物的胃癌（GC）的不可治愈性。本研究分析了111例GC患者的尿液样本。根据疾病分期和可手术性对GC队列进行分类和分析。在发现阶段，蛋白酶蛋白阵列分析鉴定了3种潜在的候选蛋白，与早期GC患者相比，晚期GC患者的尿液中升高。其中，尿激肽释放酶10（KLK 10）与肿瘤分期进展呈正相关。此外，与可手术GC患者相比，不可手术GC患者尿液中KLK 10（uKLK 10）水平显著升高（中位数，118 vs. 229; P=0.014）。uKLK 10、肿瘤位置和肿瘤大小的组合区分GC的可操作性，曲线下面积为0.859，敏感性为82.4%，特异性为86.2%。uKLK 10高表达的胃癌患者的无病生存期（DFS）明显短于uKLK 10低表达的胃癌患者（风险比：3.30 [95%可信区间，1.58-6.90] P<0.001）。免疫组化结果显示KLK 10在胃癌组织中的表达与肿瘤分期呈正相关（r=0.426，P<0.001）。此外，病理性KLK 10（pKLK 10）高表达的GC患者与pKLK 10低表达的患者相比，DFS显著缩短（风险比：3.79 [95%置信区间，1.27-11.24] P=0.010）。uKLK 10是一种有前途的非侵入性生物标志物，用于GC的不可操作性和不可治愈性。
The current imaging modalities are not sufficient to identify inoperable tumor factors, including distant metastasis and local invasion. Hence, we conducted this study using urine samples to discover non-invasive biomarkers for the incurability of gastric cancer (GC). Urine samples from 111 GC patients were analyzed in this study. The GC cohort was categorized and analyzed according to disease stage and operability. In the discovery phase, protease protein array analysis identified 3 potential candidate proteins that were elevated in the urine of advanced GC patients compared to early GC patients. Among them, urinary kallikrein 10 (KLK10) was positively associated with tumor stage progression. Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the urine of patients with inoperable GC compared to operable GC patients (median, 118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size distinguished operability of GC with an area under the curve of 0.859, 82.4% sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical analyses also demonstrated a positive correlation between tumor stage and KLK10 expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval, 1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the inoperability and incurability of GC.