Patani Neill, Jiang Wen, Mansel Robert, Newbold Robert, Mokbel Kefah
Department of Breast Surgery, St, George's University of London, London, UK.
Cancer Cell Int. 2009 Jul 30;9:18. doi: 10.1186/1475-2867-9-18.
SATB1 is a nuclear protein that has been recently reported to be a 'genome organizer' which delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. In this study, the level of mRNA expression of SATB1 and SATB2 were assessed in normal and malignant breast tissue in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters.
Breast cancer tissues (n = 115) and normal background tissues (n = 31) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period.
The levels of SATB1 were higher in malignant compared with normal breast tissue (p = 0.0167). SATB1 expression increased with increasing TNM stage (TNM1 vs. TNM2 p = 0.0264), increasing tumour grade (grade1 vs. grade 3 p = 0.017; grade 2 vs. grade 3 p = 0.0437; grade 1 vs. grade 2&3 p = 0.021) and Nottingham Prognostic Index (NPI) (NPI-1 vs. NPI-3 p = 0.0614; NPI-2 vs. NPI-3 p = 0.0495). Transcript levels were associated with oestrogen receptor (ER) positivity (ER(-) vs. ER(+) p = 0.046). SABT1 expression was also significantly correlated with downstream regulated genes IL-4 and MAF-1 (Pearson's correlation coefficient r = 0.21 and r = 0.162) and SATB2 (r = 0.506). After a median follow up of 10 years, there was a trend for higher SATB1 expression to be associated with shorter overall survival (OS). Higher levels of SATB2 were also found in malignant compared to background tissue (p = 0.049). SATB2 expression increased with increasing tumour grade (grade 1 vs. grade 3 p = 0.035). SATB2 was associated with ER positivity (ER(-) vs. ER(+) p = 0.0283) within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433).
SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SATB1 acts as a 'master genome organizer' in human breast carcinogenesis.
SATB1是一种核蛋白，最近有报道称它是一种“基因组组织者”，可在靶基因位点描绘特定的表观遗传修饰，直接上调转移相关基因，同时下调肿瘤抑制基因。在本研究中，评估了一组乳腺癌女性患者的正常和恶性乳腺组织中SATB1和SATB2的mRNA表达水平，并将其与传统临床病理参数相关联。
手术切除后立即收集乳腺癌组织（n = 115）和正常背景组织（n = 31）。提取RNA后进行逆转录，使用实时定量PCR测定转录水平，并以β-肌动蛋白表达进行标准化。将乳腺癌标本中的转录水平与正常背景组织进行比较，并根据TNM分期、淋巴结受累情况、肿瘤分级和10年随访期的临床结果进行分析。
与正常乳腺组织相比，恶性乳腺组织中SATB1水平更高（p = 0.0167）。SATB1表达随TNM分期增加而增加（TNM1与TNM2相比，p = 0.0264），随肿瘤分级增加而增加（1级与3级相比，p = 0.017；2级与3级相比，p = 0.0437；1级与2级和3级相比，p = 0.021）以及诺丁汉预后指数（NPI）增加（NPI - 1与NPI - 3相比，p = 0.0614；NPI - 2与NPI - 3相比，p = 0.0495）。转录水平与雌激素受体（ER）阳性相关（ER（-）与ER（+）相比，p = 0.046）。SABT1表达也与下游调节基因IL - 4和MAF - 1显著相关（皮尔逊相关系数r = 0.21和r = 0.162）以及SATB2（r = 0.506）。中位随访10年后，SATB1表达较高有与总生存期（OS）较短相关的趋势。与背景组织相比，恶性组织中SATB2水平也更高（p = 0.049）。SATB2表达随肿瘤分级增加而增加（1级与3级相比，p = 0.035）。在导管癌中，SATB2与ER阳性相关（ER（-）与ER（+）相比，p = 0.0283）。较高的转录水平与较差的OS显著相关（p = 0.0433）。
SATB1 mRNA表达与乳腺癌不良预后参数显著相关，包括肿瘤分级增加。SATB2 mRNA表达与肿瘤分级增加和较差的OS显著相关。这些结果与SATB1在人类乳腺癌发生中作为“主要基因组组织者”的观点一致。
