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      Zinc Finger E-box binding Homeobox 1 as Prognostic Biomarker and its Correlation with Infiltrating Immune Cells and Telomerase in Lung Cancer

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      https://www.riss.kr/link?id=A108080889

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      다국어 초록 (Multilingual Abstract)

      The aim of this study was to identify the expression of zinc finger E-box binding homeobox 1 (ZEB1), its prognostic significance, and correlation between ZEB1 and infiltrating immune cells in lung cancer. Correlation between ZEB1 and telomerase was al...

      The aim of this study was to identify the expression of zinc finger E-box binding homeobox 1 (ZEB1), its prognostic significance, and correlation between ZEB1 and infiltrating immune cells in lung cancer. Correlation between ZEB1 and telomerase was also analyzed in different types of cancers. RNA sequencing analysis and survival rates of patients were confirmed by Gene Expression Profiling Interactive Analysis (GEPIA). The Kaplan-Meier plotter and PrognoScan databases were used to analyze the prognostic value of ZEB1 in various cancers. The Tumor IMmune Estimation Resource (TIMER) was used to determine the correlation between ZEB1 and infiltrating immune cells. Lower ZEB1 expression was lower in lung cancer and was related to poor prognosis in lung adenocarcinoma (LUAD). ZEB1 expression exhibited a significantly positive correlation with infiltration levels of immune cells in LUAD and lung squamous cell carcinoma.
      Furthermore, we found that the ZEB1 expression correlated with subunits of telomerase. Our findings suggest ZEB1 as a potential biomarker to be used for prognostic significance and tumor immunology in lung cancer. The correlation between the expression of ZEB1 and telomere-related gene will help in understand the cancer-promoting mechanisms.

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      참고문헌 (Reference)

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      2 Scott CL, "ZEBs : Novel Players in Immune Cell Development and Function" 40 : 431-446, 2019

      3 Yu P, "ZEB1 stimulates breast cancer growth by up-regulating hTERT expression" 495 : 2505-2511, 2018

      4 Sanchez-Tillo E, "ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatinremodeling protein BRG1" 29 : 3490-3500, 2010

      5 Siles L, "ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression" 33 : 1368-1382, 2013

      6 Terashita K, "ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma" 69 : 593-599, 2016

      7 Sanchez-Tillo E, "ZEB1 and TCF4 reciprocally modulate their transcriptional activities to regulate Wnt target gene expression" 34 : 5760-5770, 2015

      8 Zhang P, "ZEB1 : at the crossroads of epithelialmesenchymal transition, metastasis and therapy resistance" 14 : 481-487, 2015

      9 Miyazono K, "Transforming growth factor-beta signaling in epithelial-mesenchymal transition and progression of cancer" 85 : 314-323, 2009

      10 Aigner K, "The transcription factor ZEB1(deltaEF1)promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity" 26 : 6979-6988, 2007

      1 Sanchez-Tillo E, "beta-catenin/TCF4 complex induces the epithelialto-mesenchymal transition(EMT)-activator ZEB1 to regulate tumor invasiveness" 108 : 19204-19209, 2011

      2 Scott CL, "ZEBs : Novel Players in Immune Cell Development and Function" 40 : 431-446, 2019

      3 Yu P, "ZEB1 stimulates breast cancer growth by up-regulating hTERT expression" 495 : 2505-2511, 2018

      4 Sanchez-Tillo E, "ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatinremodeling protein BRG1" 29 : 3490-3500, 2010

      5 Siles L, "ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression" 33 : 1368-1382, 2013

      6 Terashita K, "ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma" 69 : 593-599, 2016

      7 Sanchez-Tillo E, "ZEB1 and TCF4 reciprocally modulate their transcriptional activities to regulate Wnt target gene expression" 34 : 5760-5770, 2015

      8 Zhang P, "ZEB1 : at the crossroads of epithelialmesenchymal transition, metastasis and therapy resistance" 14 : 481-487, 2015

      9 Miyazono K, "Transforming growth factor-beta signaling in epithelial-mesenchymal transition and progression of cancer" 85 : 314-323, 2009

      10 Aigner K, "The transcription factor ZEB1(deltaEF1)promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity" 26 : 6979-6988, 2007

      11 Cayuela ML, "The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression" 6 : 268-274, 2005

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      16 Maitra A, "The RNA component of telomerase as a marker of biologic potential and clinical outcome in childhood neuroblastic tumors" 85 : 741-749, 1999

      17 Sahay D, "The LPA1/ZEB1/miR-21-activation pathway regulates metastasis in basal breast cancer" 6 : 20604-20620, 2015

      18 Wellner U, "The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs" 11 : 1487-1495, 2009

      19 Cristofari G, "Telomere length homeostasis requires that telomerase levels are limiting" 25 : 565-574, 2006

      20 Shen ZY, "Telomere and telomerase in the initial stage of immortalization of esophageal epithelial cell" 8 : 357-362, 2002

      21 Liu Z, "Telomerase reverse transcriptase promotes epithelial-mesenchymal transition and stem cell-like traits in cancer cells" 32 : 4203-4213, 2013

      22 Yashima K, "Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas" 57 : 2373-2377, 1997

      23 Li T, "TIMER : A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells" 77 : e108-e110, 2017

      24 Kerr KM, "Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer" 25 : 1681-1690, 2014

      25 Aghdassi A, "Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer" 61 : 439-448, 2012

      26 Chen B, "Prognostic value of ZEB-1 in solid tumors : a meta-analysis" 19 : 635-, 2019

      27 Bronsert P, "Prognostic significance of Zinc finger E-box binding homeobox 1(ZEB1)expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer" 156 : 97-108, 2014

      28 Mizuno H, "PrognoScan : a new database for meta-analysis of the prognostic value of genes" 2 : 18-, 2009

      29 Yang X, "Overexpression of zinc finger E-box binding homeobox factor 1 promotes tumor invasiveness and confers unfavorable prognosis in esophageal squamous cell carcinoma" 35 : 11977-11984, 2014

      30 Rhodes DR, "Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles" 9 : 166-180, 2007

      31 Goscinski MA, "Nuclear, cytoplasmic, and stromal expression of ZEB1 in squamous and small cell carcinoma of the esophagus" 123 : 1040-1047, 2015

      32 Sekido Y, "Molecular genetics of lung cancer" 54 : 73-87, 2003

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      35 Chen B, "JAK1 as a prognostic marker and its correlation with immune infiltrates in breast cancer" 11 : 11124-11135, 2019

      36 Kitamura T, "Immune cell promotion of metastasis" 15 : 73-86, 2015

      37 Dome JS, "High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms' tumor" 23 : 9138-9145, 2005

      38 Zhang GJ, "High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer" 5 : 564-568, 2013

      39 Hou J, "Gene expressionbased classification of non-small cell lung carcinomas and survival prediction" 5 : e10312-, 2010

      40 Tang Z, "GEPIA : a web server for cancer and normal gene expression profiling and interactive analyses" 45 : W98-W102, 2017

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      42 Ohtani H, "Focus on TILs : prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer" 7 : 4-, 2007

      43 Suzuki K, "Expression of ZEBs in gliomas is associated with invasive properties and histopathological grade" 16 : 1758-1764, 2018

      44 Sanchez-Tillo E, "Expanding roles of ZEB factors in tumorigenesis and tumor progression" 1 : 897-912, 2011

      45 Murai T, "Epithelial-tomesenchymal transition predicts prognosis in clinical gastric cancer" 109 : 684-689, 2014

      46 Chae YK, "Epithelial-mesenchymal transition(EMT)signature is inversely associated with T-cell infiltration in non-small cell lung cancer(NSCLC)" 8 : 2918-, 2018

      47 Kurahara H, "Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB1 and ZEB-2 expression in pancreatic cancer" 105 : 655-661, 2012

      48 Tsuji T, "Epithelial-mesenchymal transition and cell cooperativity in metastasis" 69 : 7135-7139, 2009

      49 Schmalhofer O, "E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer" 28 : 151-166, 2009

      50 Wu DW, "DDX3enhances oncogenic KRASinduced tumor invasion in colorectal cancer via the betacatenin/ZEB1 axis" 7 : 22687-22699, 2016

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      52 Li B, "Comprehensive analyses of tumor immunity : implications for cancer immunotherapy" 17 : 174-, 2016

      53 Zhou YM, "Clinicopathological significance of ZEB1 protein in patients with hepatocellular carcinoma" 19 : 1700-1706, 2012

      54 Yao X, "Clinicopathological significance of ZEB-1 and E-cadherin proteins in patients with oral cavity squamous cell carcinoma" 10 : 781-790, 2017

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      58 Hashiguchi M, "Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma(HCC)" 13 : 572-, 2013

      59 Singh AB, "Claudin-1 up-regulates the repressor ZEB-1 to inhibit Ecadherin expression in colon cancer cells" 41 : 2140-2153, 2011

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      61 Siegel R, "Cancer statistics. 2012" 62 : 10-29, 2012

      62 Gu Y, "CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma" 12 : 784-807, 2020

      63 Mabey Gilsenan J, "CADRE: the Central Aspergillus Data REpository 2012" 40 : D660-D666, 2012

      64 Zeisberg M, "Biomarkers for epithelial-mesenchymal transitions" 119 : 1429-1437, 2009

      65 Gyorffy B, "An online survival analysis tool to rapidly assess the effect of 22, 277 genes on breast cancer prognosis using microarray data of 1, 809 patients" 123 : 725-731, 2010

      66 Qin Y, "An hTERT/ZEB1 complex directly regulates Ecadherin to promote epithelial-to-mesenchymal transition(EMT)in colorectal cancer" 7 : 351-361, 2016

      67 Sato M, "A translational view of the molecular pathogenesis of lung cancer" 2 : 327-343, 2007

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      69 MacMahon B, "A code of ethical conduct for epidemiologists?" 44 : 147S-149S, 1991

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      2022 평가예정 재인증평가 신청대상 (재인증)
      2019-01-01 평가 등재학술지 유지 (계속평가) KCI등재
      2016-01-01 평가 등재학술지 선정 (계속평가) KCI등재
      2015-12-01 평가 등재후보로 하락 (기타) KCI등재후보
      2015-04-07 학술지명변경 외국어명 : Journal of Experimental and Biomedical Sciences -> Biomedical Science Letters KCI등재
      2011-03-29 학술지명변경 외국어명 : The Journal of Biomedical Laboratory Sciences -> Journal of Experimental and Biomedical Sciences KCI등재
      2011-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2010-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2009-01-01 평가 등재후보 1차 FAIL (등재후보1차) KCI등재후보
      2008-01-01 평가 등재후보학술지 유지 (등재후보1차) KCI등재후보
      2007-01-01 평가 등재후보학술지 유지 (등재후보1차) KCI등재후보
      2006-01-01 평가 등재후보 1차 FAIL (등재후보2차) KCI등재후보
      2005-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2003-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      2016 0.4 0.4 0.32
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      0.23 0.19 0.347 0.18
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