Background The serine protease KLK12 belongs to the human fifteen-member family of kallikrein-related peptidases. Differential expression accompanied by either increased or decreased enzymatic activity has been linked to several diseases including cancer. Triple-negative breast cancer (TNBC) represents a very aggressive subgroup of breast cancer with high tumor recurrence rates and poor patient prognosis. Here, we quantified the KLK12 mRNA expression levels in tumor tissue of TNBC patients and analyzed their prognostic value. Methods In the present study, KLK12 mRNA expression in tumor tissue of TNBC patients ( n = 116) was determined by quantitative real-time PCR assay. The association of KLK12 mRNA levels with clinical parameters, and patients’ outcome was analyzed using Chi-square tests, Cox regression models and Kaplan-Meier survival analysis. Results Positive, but low KLK12 mRNA levels were detected in about half of the cases (54 out of 116; 47%), the other samples were negative for KLK12 mRNA expression. No significant association was observed between KLK12 mRNA levels and clinicopathological variables (age, lymph node status, tumor size, and histological grade). In univariate Cox analyses, positive KLK12 mRNA expression was significantly associated with shortened disease-free survival (DFS; hazard ratio [HR] = 2.12, 95% CI = 1.19–3.78, p = 0.010) as well as overall survival (OS; HR = 1.91, 95% CI = 1.04–3.50, p = 0.037). In multivariable Cox analysis, including all clinical parameters plus KLK12 mRNA, the latter - together with age - remained an independent unfavorable predictive marker for DFS (HR = 2.33, 95% CI = 1.28–4.24, p = 0.006) and showed a trend towards significance in case of OS (HR = 1.80, 95% CI = 0.96–3.38, p = 0.066). Conclusions Positive KLK12 expression is remarkably associated with shortened DFS and OS, suggesting that KLK12 plays a tumor-supporting role in TNBC.

中文翻译：

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三阴性乳腺癌患者激肽释放酶相关肽酶12（KLK12）mRNA表达的预后价值

背景丝氨酸蛋白酶KLK12属于激肽释放酶相关肽酶的人类15个成员家族。伴随酶活性增加或减少的差异表达与包括癌症在内的多种疾病有关。三阴性乳腺癌 (TNBC) 代表了一种非常具有侵袭性的乳腺癌亚组，具有高肿瘤复发率和较差的患者预后。在这里，我们量化了 TNBC 患者肿瘤组织中的 KLK12 mRNA 表达水平并分析了它们的预后价值。方法 在本研究中，通过实时定量 PCR 法测定 TNBC 患者（n = 116）肿瘤组织中 KLK12 mRNA 的表达。KLK12 mRNA 水平与临床参数和患者结果的关联使用卡方检验、Cox 回归模型和 Kaplan-Meier 生存分析进行分析。结果 在大约一半的病例中检测到阳性但低 KLK12 mRNA 水平（116 例中的 54 例；47%），其他样品的 KLK12 mRNA 表达为阴性。KLK12 mRNA 水平与临床病理变量（年龄、淋巴结状态、肿瘤大小和组织学分级）之间未观察到显着关联。在单变量 Cox 分析中，KLK12 mRNA 阳性表达与缩短的无病生存期（DFS；风险比 [HR] = 2.12，95% CI = 1.19–3.78，p = 0.010）以及总生存期（OS；HR）显着相关= 1.91，95% CI = 1.04–3.50，p = 0.037）。在包括所有临床参数和 KLK12 mRNA 的多变量 Cox 分析中，后者 - 连同年龄 - 仍然是 DFS 的独立不利预测标志物（HR = 2.33，95% CI = 1.28-4.24，p = 0。006）并在 OS 的情况下显示出显着性趋势（HR = 1.80，95% CI = 0.96–3.38，p = 0.066）。结论 KLK12 阳性表达与 DFS 和 OS 缩短显着相关，表明 KLK12 在 TNBC 中发挥肿瘤支持作用。