Novak Kujundžić Renata, Grbeša Ivana, Ivkić Mirko, Krušlin Božo, Konjevoda Paško, Gall Trošelj Koraljka
Laboratory for Epigenomics, Ruđer Bošković Institute, Bijenička cesta 54, 10002, Zagreb, Croatia,
Pathol Oncol Res. 2014 Jul;20(3):687-95. doi: 10.1007/s12253-014-9749-y. Epub 2014 Feb 23.
BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS 7- ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival.
BORIS是一种高度保守的多功能染色质因子CTCF的旁系同源物。与已被证明具有肿瘤抑制特性的CTCF不同,BORIS属于“癌胚抗原”家族,通常仅在生殖细胞中表达,并在多种肿瘤中异常激活。BORIS表达的后果、其异构体的相对丰度及其在致癌过程中的作用尚未完全阐明。它激活了与喉癌进展相关的基因hTERT和MYC的转录。在本研究中,通过RT-PCR在转录水平和通过半定量免疫组织化学在蛋白质水平分析了32例喉鳞状细胞癌及相邻非肿瘤组织中BORIS的表达。在44%(14/32)的喉鳞状细胞癌样本中检测到了BORIS,而仅在一个正常的肿瘤相邻组织样本中检测到。使用递归划分算法mvpart进行的基于树的生存分析,提取了包含外显子7的BORIS转录变体(BORIS 7+)与缺乏外显子7的变体(BORIS 7-)的相对丰度比,作为与5年随访期内疾病复发相关的独立预后因素。BORIS 7+/BORIS 7-比率≥1的患者疾病复发率高于BORIS 7+/BORIS 7-比率<1的患者。基于Cox比例风险回归,该组的风险比为3.53。这是第一项分析BORIS蛋白和转录变体在喉鳞状细胞癌中的表达及其对复发和总生存可能的预后价值的研究。