Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Authors: Lei, Ke-Feng; Liu, Bing-Ya; Zhang, Xiao-Qing; Jin, Xiao-Long; Guo, Yan; Ye, Min; Zhu, Zheng-Gang
Abstract
Proteolytic enzymes play a key role in the metastatic stage of gastric cancer (GC). In this study, we aimed to identify the serine proteases (SPs) and their inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases of GC were initially detected by cDNA microarray. The results of the differentially expressed SPs and their inhibitor genes from the microarrays were confirmed by real-time PCR. The status of the immunohistochemical staining of the confirmed genes in patients with complete data was used to develop a survival prediction model. Finally, the prediction model was tested in different groups of GC patients. As a result, seven genes, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8, were considered as GC progression-related genes. A survival prediction model including the immunohistochemical scores of three genes and the tumor node metastasis (TNM) score was developed: Survival time (months) = 88.8607 + 2.6395 SERPINB5 - 12.0772 KILK10 + 13.7562 KLK11 - 7.0318 TNM. In conclusion, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8 were GC progression-related SPs or serpin genes. The model consisting of the expression profiles of three genes extracted from the microarray study accompanied by the TNM score accurately predicts surgery-related survival of GC patients.
A multiparametric serum kallikrein panel for diagnosis of non-small cell lung carcinoma
CLINICAL CANCER RESEARCH
Authors: Planque, Chris; Li, Lin; Zheng, Yingye; Soosaipillai, Antoninus; Reckamp, Karen; Chia, David; Diamandis, Eleftherios P.; Goodglick, Lee
Abstract
Purpose: Human tissue kallikreins are a family of 15 secreted serine proteases. We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Here, we examined the clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis. Experimental Design: Serum specimens from 51 patients with non-small cell lung cancer (NSCLC) and from 50 healthy volunteers were collected. Samples were analyzed for11 kallikreins (KLK1, KLK4-8, and KLK10-14) by specific ELISA. Data were statistically compared and receiver operating characteristic curves were constructed for each kallikrein and for various combinations. Results: Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11 and KLK12 was positively correlated with stage. With the exception of KLK5, expression of kallikreins was independent of smoking status and gender. KLK11, KLK12, KLK13, and KLK14 were associated with higher risk of NSCLC as determined by univariate analysis and confirmed by multivariate analysis. The receiver operating characteristic curve of KLK4, KLK8, KLK10, KLK11, KLK12, KLK13, and KLK14 combined exhibited an area under the curve of 0.90 (95% confidence interval, 0.87-0.97). Conclusions: We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers.