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.
Change of ranibizumab-induced human vitreous protein profile in patients with proliferative diabetic retinopathy based on proteomics analysis
CLINICAL PROTEOMICS
Authors: Zou, Chen; Han, Changjing; Zhao, Minjie; Yu, Jingjing; Bai, Lin; Yao, Yuan; Gao, Shuaixin; Cao, Hui; Zheng, Zhi
Abstract
Background: Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. Methods: A proteomic method was used to identify differentially expressed proteins in vitreous humor. Untreated PDR patients were defined as PDR group, while those who treated with intravitreal injection of ranibizumab (IVR) were defined as IVR. Gene Ontology (GO) annotation and REACTOME pathways were obtained from DAVID Bioinformatics Resources. Intravitreal level of apolipoprotein C-I (APOC1), serpin peptidase inhibitor clade A member 5 (SERPINA5), tissue inhibitor of metalloproteinases (TIMP2), and keratin 1 (KRT1) were determined by enzyme-linked immuno sorbent assay (ELISA). Results: 339 differentially expressed proteins were identified in response to IVR. The most notable GO annotation describes the altered proteins was "innate immune response". The most notable REACTOME pathway was "platelet degranulation". ELISA result showed increased level of APOC1, SERPINA5, KRT1 and a decreased level of TIMP2 in PDR group compared with IVR. Conclusions: In addition to decreasing VEGF level, ranibizumab is associated with change of human vitreous protein profile in patients with PDR, in which the differential proteins are involved in immune response, platelet degranulation, complement activation etc., suggesting that the effects of VEGF are involved in these signaling pathways.