Ghanem Tamara, Bracken James, Kasem Abdul, Jiang Wen G, Mokbel Kefah
Tamara Ghanem, James Bracken, Abdul Kasem, Kefah Mokbel, London Breast Institute, Princess Grace Hospital, London, W1U 5NY, United Kingdom.
World J Clin Oncol. 2014 May 10;5(2):156-63. doi: 10.5306/wjco.v5.i2.156.
To examine the expression of downstream of tyrosine kinase (DOK)1-6 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors.
DOK1-6 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 112) and normal background breast tissue (n = 31). Tissues were collected between 1991 and 1996 at two centres and all patients underwent mastectomy and ipsilateral axillary node dissection. All tissues were randomly numbered and the details were only made known after all analyses were completed. Transcript levels of expression were determined using real-time polymerase chain reaction and analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period.
DOK-2 and DOK-6 expression decreased with increasing TNM stage. DOK-6 expression decreased with increasing Nottingham Prognostic Index (NPI) [NPI-1 vs NPI-3 (mean copy number 15.4 vs 0.22, 95%CI: 2.7-27.6, P = 0.018) and NPI-2 vs NPI-3 (mean copy number 7.6 vs 0.22, 95%CI: 0.1-14.6, P = 0.048)]. After a median follow up period of 10 years, higher levels of DOK-2 expression were found among patients who remained disease-free compared to those who developed local or distant recurrence (mean copy number 3.94 vs 0.0000096, 95%CI: 1.0-6.85, P = 0.0091), and distant recurrence (mean copy number 3.94 vs 0.0025, 95%CI: 1.0-6.84, P = 0.0092). Patients who remained disease-free had higher levels of DOK-6 expression compared to those who died from breast cancer.
Decreasing expression levels of DOK-2 and DOK-6 with increased breast tumour progression supports the notion that DOK-2 and DOK-6 behave as tumour suppressors in human breast cancer.
检测酪氨酸激酶下游（DOK）1 - 6基因在正常乳腺组织和乳腺癌组织中的表达情况，并将其与多种临床病理及预后因素相关联。
对新鲜冷冻的乳腺癌组织样本（n = 112）和正常乳腺背景组织（n = 31）进行DOK1 - 6 mRNA提取及逆转录。组织于1991年至1996年在两个中心收集，所有患者均接受了乳房切除术和同侧腋窝淋巴结清扫术。所有组织均随机编号，所有分析完成后才公布详细信息。使用实时聚合酶链反应测定转录本表达水平，并针对TNM分期、肿瘤分级及10年随访期内的临床结局进行分析。
DOK - 2和DOK - 6的表达随TNM分期增加而降低。DOK - 6的表达随诺丁汉预后指数（NPI）增加而降低[NPI - 1与NPI - 3（平均拷贝数15.4对0.22，95%CI：2.7 - 27.6，P = 0.018）以及NPI - 2与NPI - 3（平均拷贝数7.6对0.22，95%CI：0.1 - 14.6，P = 0.048）]。中位随访期10年后，与出现局部或远处复发的患者相比，无疾病复发患者的DOK - 2表达水平更高（平均拷贝数3.94对0.0000096，95%CI：1.0 - 6.85，P = 0.0091），与远处复发患者相比亦如此（平均拷贝数3.94对0.0025，95%CI：1.0 - 6.84，P = 0.0092）。与死于乳腺癌的患者相比，无疾病复发患者的DOK - 6表达水平更高。
随着乳腺肿瘤进展，DOK - 2和DOK - 6表达水平降低，这支持了DOK - 2和DOK - 6在人类乳腺癌中作为肿瘤抑制因子的观点。
