Anti-KDR monoclonal antibody

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non-cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture-based next-generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm-level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non-cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFR alpha) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.

Introduction: Yupingfengsan () is a classical traditional Chinese formulae with proven therapeutic effect on the disease of respiratory system. However, its action mechanism remains obscure for lung adenocarcinoma (LAD). This study aimed to investigate the potential target genes and the mechanism of Yupingfengsan in the treatment of LAD. Methods: Yupingfengsan chemical ingredients and related targets were predicted by public databases. Differential expression genes of LAD were obtained from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was used to execute gene ontology function and pathway enrichment analysis. The protein interaction network was constructed by Cytoscape. Finally, potential target genes and mechanism of Yupingfengsan on LAD were predicted. The differential expression and prognostic analysis of target genes were verified by TCGA database and the Kaplan-Meier plotter, respectively. Results: A total of 253 targets from 30 active ingredients of Yupingfengsan were predicted. 4426 DEGs were identified from TCGA LAD data sets. 32 upregulated and 52 downregulated genes were obtained between Yupingfengsan putative targets and DEGs of LAD. MAPK, VEGF, and ErbB signaling pathways seemed to be the most likely mechanism. 6 potential target genes, PLA2G4A, PRKCB, PIK3R1, KDR, PLA2G1B and PTGS2 were extracted. These 6 candidates were verified significantly different expression between LAD and paired adjacent normal tissues, and PRKCB, PIK3R1, KDR, PLA2G1B suggested a significant correlation with LAD prognosis. Conclusion: Differentially expressed in tumors, PLA2G4A, PRKCB, PIK3R1, KDR, PLA2G1B and PTGS2 are potential therapeutic targets of Yupingfengsan in the treatment of LAD, and MAPK, VEGF and ErbB signaling pathways are involved.