Identification of target gene of venous thromboembolism in patients with lymphoma via microarray analysis

Liu,Pengfei; Jiang,Wenhua; Zhang,Huilai

doi:10.3892/ol.2017.6625

Identification of target gene of venous thromboembolism in patients with lymphoma via microarray analysis

Authors:
- Pengfei Liu
- Wenhua Jiang
- Huilai Zhang
View Affiliations

Affiliations: Department of Lymphoma, Sino‑US Center of Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China, Department of Radiotherapy, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
Published online on: July 20, 2017 https://doi.org/10.3892/ol.2017.6625
Pages: 3313-3318
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Patients with lymphoma are at high risk of developing venous thromboembolism (VTE). The purpose of the present study was to identify the target gene associated with VTE for patients with lymphoma. Microarray data was downloaded from the gene expression omnibus database (GSE17078), which comprised the control group, 27 normal blood outgrowth endothelial cell (BOEC) samples, and the case group, 3 BOEC samples of venous thrombosis with protein C deficiency. Differentially expressed genes (DEGs) were identified by the Limma package of R. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed via the database for annotation, visualization and integrated discovery. Differentially coexpressed pairs were identified by the DCGL package of R. The subsequent protein‑protein interaction (PPI) networks and gene coexpression networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins database, and were visualized by Cytoscape software. A total of 110 DEGs were obtained, including 73 upregulated and 37 downregulated genes. GO and KEGG pathway enrichment analyses identified 132 significant GO terms and 9 significant KEGG pathways. In total, 97 PPI pairs for PPI network and 309 differential coexpression pairs for the gene coexpression network were obtained. Additionally, the connective tissue growth factor (CTGF) gene was closely connected with other genes in the two networks. A total of 2 KEGG pathways were associated with VTE and CTGF may be the target gene of VTE in patients with lymphoma. The present study may identify the molecular mechanism of VTE, but additional clinical study is required to validate the results.

View Figures

View References

1	Khorana AA, Francis CW, Culakova E, Kuderer NM and Lyman GH: Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 110:2339–2346. 2007. View Article : Google Scholar : PubMed/NCBI
2	Wun T and White RH: Venous thromboembolism in patients with acute leukemia, lymphoma and multiple myeloma. Thromb Res. 125:(Suppl 2). S96–S102. 2010. View Article : Google Scholar : PubMed/NCBI
3	Zhou X, Teegala S, Huen A, Ji Y, Fayad L, Hagemeister FB, Gladish G and Vadhan-Raj S: Incidence and risk factors of venous thromboembolic events in lymphoma. Am J Med. 123:935–941. 2010. View Article : Google Scholar : PubMed/NCBI
4	Khalil J, Bensaid B, Elkacemi H, Afif M, Bensaid Y, Kebdani T and Benjaafar N: Venous thromboembolism in cancer patients: An underestimated major health problem. World J Surg Oncol. 13:2042015. View Article : Google Scholar : PubMed/NCBI
5	Mohren M, Markmann I, Jentsch-Ullrich K, Koenigsmann M, Lutze G and Franke A: Increased risk of thromboembolism in patients with malignant lymphoma: A single-centre analysis. Br J Cancer. 92:1349–1351. 2005. View Article : Google Scholar : PubMed/NCBI
6	Cushman M: Epidemiology and risk factors for venous thrombosis. Semin Hematol. 44:62–69. 2007. View Article : Google Scholar : PubMed/NCBI
7	Zheng RL, Jiang YJ and Wang X: Role of microRNAs on therapy resistance in Non-Hodgkin's lymphoma. Int J Clin Exp Med. 7:3818–3832. 2014.PubMed/NCBI
8	Benson N, Whipple M and Kalet IJ: A Markov model approach to predicting regional tumor spread in the lymphatic system of the head and neck. AMIA Annu Symp Proc. 2006:31–35. 2006.
9	Kewitz S, Kurch L, Volkmer I and Staege MS: Stimulation of the hypoxia pathway modulates chemotherapy resistance in Hodgkin's lymphoma cells. Tumor Biol. 37:8229–8237. 2016. View Article : Google Scholar
10	Blom JW, Doggen CJ, Osanto S and Rosendaal FR: Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 293:715–722. 2005. View Article : Google Scholar : PubMed/NCBI
11	Goldschmidt N, Linetsky E, Shalom E, Varon D and Siegal T: High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer. 98:1239–1242. 2003. View Article : Google Scholar : PubMed/NCBI
12	Caruso V, Di Castelnuovo A, Meschengieser S, Lazzari MA, de Gaetano G, Storti S, Iacoviello L and Donati MB: Thrombotic complications in adult patients with lymphoma: A meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events. Blood. 115:5322–5328. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ikeda M, Kan-No H, Hayashi M, Tsukada H, Shida M, Hirasawa T, Muramatsu T, Ogushi Y and Mikami M: Predicting perioperative venous thromboembolism in Japanese gynecological patients. PLoS One. 9:e892062014. View Article : Google Scholar : PubMed/NCBI
14	Boersma RS, Hamulyak K, Cate HT and Schouten HC: Congenital thrombophilia and central venous catheter-related thrombosis in patients with cancer. Clin Appl Thromb/Hemost. 16:643–649. 2010. View Article : Google Scholar
15	Achkar A, Horellou MH, Leclercq X, Lambert Y, Conard J, Laaban JP and Samama MM: PO73 prevalence of cancer and congenital thrombophilia in 435 patients with acute venous thromboembolism (VTE). Thromb Res. 120:(Suppl 2). S1682007. View Article : Google Scholar
16	Liu BH, Yu H, Tu K, Li C, Li YX and Li YY: DCGL: An R package for identifying differentially coexpressed genes and links from gene expression microarray data. Bioinformatics. 26:2637–2638. 2010. View Article : Google Scholar : PubMed/NCBI
17	Khorana AA, Kuderer NM, Culakova E, Lyman GH and Francis CW: Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 111:4902–4907. 2008. View Article : Google Scholar : PubMed/NCBI
18	Korte W: Cancer and thrombosis: An increasingly important association. Support Care Cancer. 16:223–228. 2008. View Article : Google Scholar : PubMed/NCBI
19	Rodriguez AO, Wun T, Chew H, Zhou H, Harvey D and White RH: Venous thromboembolism in ovarian cancer. Gynecol Oncol. 105:784–790. 2007. View Article : Google Scholar : PubMed/NCBI
20	Semrad TJ, O'Donnell R, Wun T, Chew H, Harvey D, Zhou H and White RH: Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosur. 106:601–608. 2007. View Article : Google Scholar
21	Franchini M: Thromboembolic risk in hematological malignancies. Clin Chem Lab Med. 53:1139–1147. 2015. View Article : Google Scholar : PubMed/NCBI
22	Falanga A, Marchetti M and Russo L: Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol. 24:702–710. 2012. View Article : Google Scholar : PubMed/NCBI
23	Elice F and Rodeghiero F: Hematologic malignancies and thrombosis. Thromb Res. 129:360–366. 2012. View Article : Google Scholar : PubMed/NCBI
24	Kunisawa J and Kiyono H: Alcaligenes is commensal bacteria habituating in the gut-associated lymphoid tissue for the regulation of intestinal IgA responses. Front Immunol. 3:652012. View Article : Google Scholar : PubMed/NCBI
25	Avula LR, Knapen D, Buckinx R, Vergauwen L, Adriaensen D, Van Nassauw L and Timmermans JP: Whole-genome microarray analysis and functional characterization reveal distinct gene expression profiles and patterns in two mouse models of ileal inflammation. BMC Genomics. 13:3772012. View Article : Google Scholar : PubMed/NCBI
26	Wang L and Wu X: Cytokines of defender against cell death 1 and allograft inflammatory factor-1 with regard to innate immunity of fish. J Fisher Sci Chin. 18:237–242. 2013. View Article : Google Scholar
27	Ghasemi S, Tavakoli A, Moghadam M, Zargar MA, Abbaspour M, Hatamnejadian N and Ebrahimi A: Risk of prostate cancer and thrombosis-related factor polymorphisms. Biomed Rep. 2:53–56. 2014.PubMed/NCBI
28	Sarajlić A, Janjić V, Stojković N, Radak D and Pržulj N: Network topology reveals key cardiovascular disease genes. PLoS One. 8:e715372013. View Article : Google Scholar : PubMed/NCBI
29	von Mering C, Krause R, Snel B, Cornell M, Oliver SG, Fields S and Bork P: Comparative assessment of large-scale data sets of protein-protein interactions. Nature. 417:399–403. 2002. View Article : Google Scholar : PubMed/NCBI
30	Gaiteri C, Ding Y, French B, Tseng GC and Sibille E: Beyond modules and hubs: The potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders. Genes Brain Behav. 13:13–24. 2014. View Article : Google Scholar : PubMed/NCBI
31	Sharan R, Ulitsky I and Shamir R: Network-based prediction of protein function. Mol Syst Biol. 3:882007. View Article : Google Scholar : PubMed/NCBI
32	Yook SH, Oltvai ZN and Barabási AL: Functional and topological characterization of protein interaction networks. Proteomics. 4:928–942. 2004. View Article : Google Scholar : PubMed/NCBI
33	Horvath S and Dong J: Geometric interpretation of gene coexpression network analysis. PLoS Comput Biol. 4:e10001172008. View Article : Google Scholar : PubMed/NCBI
34	Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B and Peyvandi AA: Protein-protein interaction networks (PPI) and complex diseases. Gastroenterol Hepatol Bed Bench. 7:17–31. 2014.PubMed/NCBI
35	Jun JI and Lau LF: Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov. 10:945–963. 2011. View Article : Google Scholar : PubMed/NCBI
36	Hall-Glenn F and Lyons KM: Roles for CCN2 in normal physiological processes. Cell Mol Life Sci. 68:3209–3217. 2011. View Article : Google Scholar : PubMed/NCBI
37	de Winter P, Leoni P and Abraham D: Connective tissue growth factor: Structure-function relationships of a mosaic, multifunctional protein. Growth Factors. 26:80–91. 2008. View Article : Google Scholar : PubMed/NCBI
38	Yin D, Chen W, O'Kelly J, Lu D, Ham M, Doan NB, Xie D, Wang C, Vadgama J, Said JW, et al: Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme. Int J Cancer. 127:2257–2267. 2010. View Article : Google Scholar : PubMed/NCBI
39	Leask A and Abraham DJ: All in the CCN family: Essential matricellular signaling modulators emerge from the bunker. J Cell Sci. 119:4803–4810. 2006. View Article : Google Scholar : PubMed/NCBI
40	Brigstock DR: Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: Lessons from transgenic animals. J Cell Commun Signal. 4:1–4. 2010. View Article : Google Scholar : PubMed/NCBI
41	Koshman YE, Patel N, Chu M, Iyengar R, Kim T, Ersahin C, Lewis W, Heroux A and Samarel AM: Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure. J Card Fail. 19:283–294. 2013. View Article : Google Scholar : PubMed/NCBI
42	Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A, Takigawa M, Nakanishi T and Takehara K: Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol. 181:153–159. 1999. View Article : Google Scholar : PubMed/NCBI
43	Charrier A and Brigstock DR: Regulation of pancreatic function by connective tissue growth factor (CTGF, CCN2). Cytokine Growth Factor Rev. 24:59–68. 2013. View Article : Google Scholar : PubMed/NCBI
44	Aikawa T, Gunn J, Spong SM, Klaus SJ and Korc M: Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther. 5:1108–1116. 2006. View Article : Google Scholar : PubMed/NCBI
45	Sala-Torra O, Gundacker HM, Stirewalt DL, Ladne PA, Pogosova-Agadjanyan EL, Slovak ML, Willman CL, Heimfeld S, Boldt DH and Radich JP: Connective tissue growth factor (CTGF) expression and outcome in adult patients with acute lymphoblastic leukemia. Blood. 109:3080–3083. 2007.PubMed/NCBI
46	Lee AY and Levine MN: Venous thromboembolism and cancer: Risks and outcomes. Circulation. 107:(23 Suppl 1). I17–I21. 2003. View Article : Google Scholar : PubMed/NCBI