Diagnostic role of Wnt pathway gene promoter methylation in non-small-cell lung cancer
CHENG Guangjia1, LIU Shunlin2, ZHU Guoliang3, WANG Jinzhi4.
1.Department of Geriatrics, Fenghua People’s Hospital, Ningbo, 315500; 2.Department of Respiratory, the First Affiliated Hospital of Soochow University, Suzhou, 215600; 3.Department of Pathology, Huzhou First People’s Hospital, Huzhou, 313000; 4.Department of Cell Biology School of Medicine, Soochow University, Suzhou, 215007
CHENG Guangjia,LIU Shunlin,ZHU Guoliang, et al. Diagnostic role of Wnt pathway gene promoter methylation in non-small-cell lung cancer[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2018, 48(7): 499-503.
Abstract:Objective: The gene in the Wnt signaling pathway was analyzed to improve its role as a biomarker for the diagnosis of non-small-cell lung cancer (NSCLC). Methods: The methylation levels of SFRP1, SFRP2, WIF1 and PRKCB in 111 NSCLC patients were evaluated by quantitative methylation-specific PCR (qMSP), and combined with clinical data and TCGA database analysis. Results: Promoter methylation levels of four candidate genes were significantly higher in tumor tissues compared with the adjacent tissues. SFRP1, SFRP2 expression level in male patients was higher than female; the sensitivity and specificity were 83.3% and 96.0% combined with the methylation level of four in the diagnosis of NSCLC. Conclusion: A panel of Wnt signal pathway genes (SFRP1, SFRP2, WIF1 and PRKCB) had the potential as methylation biomarkers in the diagnosis of NSCLC.
[1] XIE J, ZHANG Y, HU X, et al. Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer[J]. Med Oncol, 2015, 32(5): 145.
[2] LEE S H, CHEN T, ZHOU J, et al. Protein kinase C-beta gene variants, pathway activation, and enzastaurin activity in lung cancer[J]. Clin Lung Cancer, 2010, 11(3): 169-175.
[3] ANGLIM P P, ALONZO T A, LAIRD-OFFRINGA I A. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: An update[J]. Mol Cancer, 2008, 7: 81.
[4] DI P A, DEL R M, PETRINI I, et al. Recent advances in epigenomics in NSCLC: real-time detection and therapeutic implications[J]. Epigenomics, 2016, 8(8): 1151-1167.
[5] MEHTA A, DOBERSCH S, ROMERO-OLMEDO A J, et al. Epigenetics in lung cancer diagnosis and therapy[J]. Cancer Metastasis Rev, 2015, 34(2): 229-241.
[6] SCHNEIDER J, PHILIPP M, VELCOVSKY H G, et al. Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19-fragments (CYFRA 21-1) in patients with lung cancer in comparison to other lung diseases[J]. Anticancer Res, 2003, 23(2A): 885-893.
[7] REYA T, CLEVERS H. Wnt signalling in stem cells and cancer[J]. Nature, 2005, 434(7035): 843-850.
[8] YU J, TAO Q, CHENG Y Y, et al. Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer[J]. Cancer, 2009, 115 (7): 49-60.
[9] LIANG J, KANG X, HALIFU Y, et al. Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis[J]. BMC Cancer, 2015, 15: 641.
[10] LIU J B, QIANG F L, DONG J, et al. Plasma DNA methylation of Wnt antagonists predicts recurrence of esophageal squamous cell carcinoma[J]. World J Gastroenterol, 2011, 17(44): 4917-4921.
[11] GHASEMI A, ROSTAMI S, CHAHARDOULI B, et al. Study of SFRP1 and SFRP2 methylation status in patients with de novo acute myeloblastic leukemia[J]. Int J Hematol Oncol Stem Cell Res, 2015, 9(1): 15-21.
[12] KOHNO H, AMATYA V J, TAKESHIMA Y, et al. Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma[J]. Oncol Rep, 2010, 24(2): 423-431.
[13] SUZUKI M, SHIGEMATSU H, NAKAJIMA T, et al. Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer[J]. Clin Cancer Res, 2007, 13(20): 6087-6092.
[14] BERARDI R, MORGESE F, SANTINELLI A, et al. Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex[J]. Oncotarget, 2016, 7(50): 82648-82657.
[15] LEE S M, PARK J Y, KIM D S. Wif1 hypermethylation as unfavorable prognosis of non-small cell lung cancers with EGFR mutation[J]. Mol Cells, 2013, 36(1): 69-73.
[16] HUANG T, CHEN X, HONG Q, et al. Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients[J]. Sci Rep, 2015, 5: 8897.
[17] LI H, WEINSTEIN I B. Protein kinase C beta enhances growth and expression of cyclin D1 in human breast cancer cells[J]. Cancer Res, 2006, 66(23): 11399-11408.
[18] ABRAMS S T, LAKUM T, LIN K, et al. B-cell receptor signaling in chronic lymphocytic leukemia cells is regulated by overexpressed active protein kinase CbetaII[J]. Blood, 2007, 109(3): 1193-1201.