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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Clinical significance of serum cathepsin B and cystatin C levels and their ratio in the prognosis of patients with esophageal cancer

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          Abstract

          Objective

          The main purpose of this study was to analyze the serum cathepsin B (CTSB) and cystatin C (CysC) levels in patients with esophageal carcinoma and their correlation with the clinical indices and prognosis.

          Methods

          The serum levels of CTSB and CysC from 56 patients with esophageal carcinoma and 30 healthy donors were determined preoperatively by using enzyme-linked immunosor-bent assay. The correlation between CTSB and CysC was evaluated by Spearman correlation coefficient test. Kaplan–Meier survival curves were plotted, while the survival rates were compared using the log-rank test. Univariate and multivariate analyses of prognostic factors for survival were performed using the Cox proportional hazard regression model with a 95% confidence interval.

          Results

          CTSB (38.35±4.3 ng/mL) and CysC (703.96±23.6 ng/mL) levels were significantly higher in the sera of the patients than in controls. A significant correlation was observed between CTSB and CysC ( r=0.754, P<0.001). The levels of CTSB and CysC/CTSB in the patient serum significantly correlated with the T status. CysC/CTSB ratio was also found to be significantly correlated with lymph node metastasis. None of the parameters were observed to be related to CysC, including age, gender, pathologic type, tumor differentiation and tumor invasion depth. Kaplan–Meier analysis showed that patients with higher levels of CysC/CTSB and negative lymph node metastasis experienced significantly longer overall survival time, whereas patients with higher CSTB levels tended to live shorter, although the difference was not statistically significant ( P=0.081).

          Conclusion

          Serum CTSB and CysC levels are of diagnostic significance in esophageal cancer. The ratio of serum CysC/CTSB is prognostic for the survival of esophageal carcinoma patients.

          Most cited references33

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          MEROPS: the database of proteolytic enzymes, their substrates and inhibitors

          Peptidases, their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.ac.uk) aims to fulfill the need for an integrated source of information about these. The database has hierarchical classifications in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families, which are in turn grouped into clans. Recent developments include the following. A community annotation project has been instigated in which acknowledged experts are invited to contribute summaries for peptidases. Software has been written to provide an Internet-based data entry form. Contributors are acknowledged on the relevant web page. A new display showing the intron/exon structures of eukaryote peptidase genes and the phasing of the junctions has been implemented. It is now possible to filter the list of peptidases from a completely sequenced bacterial genome for a particular strain of the organism. The MEROPS filing pipeline has been altered to circumvent the restrictions imposed on non-interactive blastp searches, and a HMMER search using specially generated alignments to maximize the distribution of organisms returned in the search results has been added.
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            Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray.

            To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.
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              Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis.

              The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2017
                03 April 2017
                : 10
                : 1947-1954
                Affiliations
                [1 ]Department of Oncology
                [2 ]Department of Thoracic Surgery
                [3 ]Department of Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China
                Author notes
                Correspondence: Qingxia Fan; Liping Wang, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No 1 Jianshe East Road, Zhengzhou 450052, People’s Republic of China, Tel +86 371 6629 5532; +86 371 6629 5552, Email nnty1608@ 123456163.com ; wlp@ 123456zzu.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                ott-10-1947
                10.2147/OTT.S123042
                5388217
                28435284
                4a149cfe-7fba-461b-be32-7e5cd726147a
                © 2017 Yan et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                esophageal squamous cell carcinoma,cathepsin b,cystatin c,diagnostic value,prognosis

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