Analysis On MMP-7 Expression And Its Bioinformatics In Renal Cell Carcinoma

BackgroundRenal cell carcinoma(RCC)is one of the most common malignant tumors in adult kidney,and RCC's incidence and mortality have been increasing with the development of society and economy and the improvement of living standards.Currently,even though some progress has been made in surgical treatment and biotherapy,RCC is featured with easily late detection,rapid development,early metastasis and poor prognosis,which affects patients' life quality.Therefore,further research on RCC-related genes is significant for discussion of occurrence mechanism of RCC and early diagnosis and treatment of RCC.ObjectiveThe purpose of this study is to discuss the role of matrilysin(MMP-7)and microvessel density(MVD)in invasion and metastasis of RCC,to deeply explore molecular and physiological mechanism of metastasis of RCC,and to primarily build regulatory network model of RCC-related genes,aiming to provide certain theoretical evidence for targeted therapy of RCC in clinic.Materials and methods1.80 cases of patients receiving RCC surgical treatment at the urology department of Affiliated Cancer Hospital of Zhengzhou University from March 2014 to October 2015 were collected in this study(50 males,30 females,20-76 years of age)for their renal clear cell carcinoma tissue specimen,because they were all diagnosed by pathological examination and had completely clinical data.Tumor Node Metastasis(TNM): stage(TNM)I(24 cases),stage(TNM)II(21 cases),stage(TNM)III(18 cases)and stage(TNM)IV(7 cases);Fuhrman classification: class I(20 cases),class II(28 cases),class III(24 cases)and class IV(4 cases);Immunohistochemical S-P method was used to detect MMP-7 expression and MVD expression in 80 cases of RCC tissue and adjacent normal tissues.And SPSS21.0software was adopted to analyze the relations between expression of MMP-7 and MVD and clinical characteristics and correlation between MMP-7 expression and MVD expression.2.With MMP-7 protein as studying subject,bioinformatics method was used to analyze its animo acid composition,transmembrane structure,coiled-coils,subcellular localization,signal peptide,functions and all structures.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)were employed to conduct functional analysis(by GO)and signaling pathway analysis on RCC-related genes including p53,PTEN,MMP-9,KISS-1,MMP-7 and VHL,and finally a primary RCC regulatory network.ResultsExpression rate of MMP-7 in RCC tissue and adjacent normal tissues were65.00% and 25.00%,respectively;MVD mean in RCC tissue and adjacent normal tissues were respectively(147.53 ± 32.72)and(53.17 ± 11.87).According to comparison of MMP-7 and MVD in RCC tissue and adjacent normal tissues,the difference was statistically significant(P<0.05);different expression of MMP-7 andMVD in RCC tissue were linked to clinical stages,pathological grade,tumor size,renal capsule invasion and lymph node metastasis(P<0.05)and not to patient's age and gender(P>0.05,without statistical significance);MVD value in MMP-7 positive patient was apparently higher than that in MMP-7 negative patient,which indicates that there's a positive correlation between MMP-7 positive expression and MVD.2.MMP-7 gene consists of 1131 bp including coding region and non-coding region,and the former encodes a polypeptide with 267 animo acids which develops into an supercoiling mainly by random coils and alpha helices,forming an stable hydrophilic neutral protein.Analyzing for subcellular localization indicated that this protein owns secretion pathway which is located outside the cell.And 1-17 thanimo acid of N terminus is the splicing sites of signaling peptides and mature polypeptide starts from the 18 th animo acid,showing that this protein belongs to secretory protein.Through functional structure domain analysis,it's found that MMP-7 protein contains two functional domains: PG binding domain and zinc finger binding domain,and that its co-crosslinkable proteins are also the correlative proteins to cell proliferation and metastasis.3.Based on GO functional analysis and KEGG signaling pathway analysis,a primary RCC regulatory network model composed of seven gene markers including p53,PTEN,MMP-9,KISS-1,MMP-7,VHL and VEGF,and of other correlative genes was established.ConclusionsMMP-7 is closely related to angiogenesis and the combined detection of MVD and MMP-7 is valuable for the evaluation,metastasis and prognosis of RCC malignant degree;MMP-7 is one of secretary proteins and its co-crosslinkable proteins are correlated to cancer cell proliferation and metastasis;a preliminary apoptosis regulatory network of renal carcinoma cells involving p53,PTEN,MMP-9,KISS-1,MMP-7 and VHL genes markers has been built in this study and these included genes markers can be decided as potential therapeutic targets for renalcarcinoma.