The online version of this article (https://doi.org/10.1186/s12885-017-3810-7) contains supplementary material, which is available to authorized users.
Wenting Huang and Xuemin Xue are co-first authors
Jianming Ying and Ning Lv are co-senior authors
PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL.
One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification. Their methylation status of PCDH10 promoter were accessed by methylation-specific PCR (MSP) with methylated and unmethylated primers. Analysis of overall survival and clinicopathological correlation were conducted.
PCDH10 hypermethylation were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive lymph node/follicular hyperplasia. In RCHOP-treated cohort, promoter methylation of PCDH10 is an independent prognostic indicator of worse overall survival (p = 0.017; HR 4.045; 95%CI 1.287–12.711) and worse progress-free survival (p = 0.014; HR 2.977; 95%CI 1.245–7.119). Whereas, PCDH10 hypermethylation wasn’t correlated with MYC translocation and cell of origin classification using Hans model.
PCDH10 methylation status could serve as a valuable biomarker for risk classification, and a potential therapeutic target for demethylating drugs in DLBCL in the future.
Additional file 1: Table S1. The clinicopathological characteristics and PCDH10 methylation status of 107 cases are showed in this table. (XLS 32 kb)12885_2017_3810_MOESM1_ESM.xls
Additional file 2: Table S2. The details of survival (OS and PFS) and other clinicopathological characteristics of 65 RCHOP-treated cases are showed in this table. (XLS 40 kb)12885_2017_3810_MOESM2_ESM.xls
Additional file 3: Diagram S1. Description: The location of the primers in relation to the PCDH10 promoter and start site. (PPTX 194 kb)12885_2017_3810_MOESM3_ESM.pptx
Kim SY, Yasuda S, Tanaka H, Yamagata K, Kim H. Non-clustered protocadherin. Cell Adhes Migr. 2011;5(2):97–105. CrossRef
Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan AT, Tao Q. Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene. 2006;25(7):1070–80. CrossRefPubMed
Hou YC, Deng JY, Zhang RP, Xie XM, Cui JL, WP W, Hao XS, Liang H. Evaluating the clinical feasibility: the direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer. Cancer Biomarkers. 2015;15(5):567–73. CrossRefPubMed
Narayan G, Xie D, Freddy AJ, Ishdorj G, Do C, Satwani P, Liyanage H, Clark L, Kisselev S, Nandula SV, et al. PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis. Genes Chromosomes Cancer. 2013;52(11):1030–41. CrossRefPubMed
Bognar MK, Vincendeau M, Erdmann T, Seeholzer T, Grau M, Linnemann JR, Ruland J, Scheel CH, Lenz P, Ott G, et al. Oncogenic CARMA1 couples NF-kappaB and beta-catenin signaling in diffuse large B-cell lymphomas. Oncogene. 2016;
Ge X, Lv X, Feng L, Liu X, Wang X. High expression and nuclear localization of beta-catenin in diffuse large B-cell lymphoma. Mol Med Rep. 2012;5(6):1433–7. PubMed
Lopez-Guillermo A, Colomo L, Jimenez M, Bosch F, Villamor N, Arenillas L, Muntanola A, Montoto S, Gine E, Colomer D, et al. Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(12):2797–804. CrossRef
- Clinical significance of PCDH10 promoter methylation in diffuse large B-cell lymphoma
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II