Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstr, 2-8, 72076, Tuebingen, Germany.
BMC Cancer. 2013 Dec 4;13:569. doi: 10.1186/1471-2407-13-569.
Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumor cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies.
Expression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74).
Positive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC.EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity.
The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. Further prospective trials are warranted to validate this new concept for the diagnosis of neoplasia and tumor recurrence.
能够用于表征口腔鳞状细胞癌（OSCC）或其他类型的癌的恶性肿瘤和治疗反应的生物标志物仍然存在很大的需求。生物化学自杀分子核酸内切酶 DNaseX（DNaseI 样 1）已被用于鉴定 Apo10 蛋白表位，该表位标记了具有异常凋亡和增殖的肿瘤细胞。转酮醇酶样蛋白 1（TKTL1）代表了即使在存在氧气的情况下（有氧糖酵解/Warburg 效应），无氧葡萄糖代谢的酶学基础，这与侵袭性生长/转移和对激进和凋亡诱导治疗的抗性相关的更恶性表型同时发生。
通过免疫组织化学法回顾性分析了 161 例 OSCC 标本中 Apo10 和 TKTL1 的表达。这两种标志物均代表不良生存的独立标志物。此外，前瞻性地将 Apo10 和 TKTL1 用于 OSCC（n=50）、乳腺癌（n=48）、前列腺癌（n=115）患者和献血者/对照者（n=74）的 EDIM-血液检测中的表位检测。
阳性 Apo10 和 TKTL1 表达与肿瘤的复发相关。多变量分析表明，Apo10 和 TKTL1 表达是肿瘤特异性生存降低的独立预后因素。Apo10+/TKTL1+亚组在 OSCC 中表现出最差的无病生存率。EDIM-Apo10 和 EDIM-TKTL1 血液检测能够在手术前和手术后的护理中敏感而特异性地检测到 OSCC、乳腺癌和前列腺癌患者。Apo10+/TKTL1+联合评分可检测出独立于肿瘤实体的 95.8%的敏感性和 97.3%的特异性。
通过两种生物标志物 Apo10 和 TKTL1 联合检测两个独立的基本生物物理过程，可以以非侵入性和具有成本效益的方式敏感而特异性地检测肿瘤。需要进一步的前瞻性试验来验证这一用于诊断肿瘤和肿瘤复发的新概念。
