III, Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
BMC Cancer. 2011 Aug 19;11:363. doi: 10.1186/1471-2407-11-363.
For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R) and Transketolase-like-1 (TKTL1) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.
Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.
Significantly higher expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High TKTL1 expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.
High TKTL-1 expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.
对于局部晚期直肠癌（LARC）患者，新辅助放化疗被推荐为标准治疗。迄今为止，尚未确定接受多模式治疗的患者的预测或预后分子因素。在癌症中，增加的血管生成和改变的肿瘤代谢作为对缺氧条件的适应，在肿瘤进展和转移中发挥重要作用。血管内皮生长因子受体（VEGF-R）和转酮醇酶样-1（TKTL1）的表达增强与肿瘤中的缺氧条件有关。在寻找潜在的预后分子标志物时，我们研究了接受新辅助放化疗和西妥昔单抗治疗的 LARC 患者中 VEGFR-1、VEGFR-2 和 TKTL1 的表达。
对 33 例局部晚期直肠癌患者（男性 23 例，女性 10 例；中位年龄：61 岁）的治疗前活检肿瘤和相应的正常组织进行分析，这些患者接受了 I 期和 II 期新辅助放化疗（西妥昔单抗、伊立替康、卡培他滨联合放疗）试验。采用定量 PCR 分析。
与相应的正常组织相比，治疗前活检和新辅助放化疗后切除标本中的肿瘤组织中 VEGFR-1/2 的表达明显更高。高 TKTL1 表达与无病生存显著相关。没有一种标志物对肿瘤回归分级等早期反应参数有影响。所研究标志物之间的基因表达无相关性。
在接受强化新辅助放化疗的 LARC 患者中，高 TKTL-1 表达与无病生存率相关，因此可能作为一种分子预后标志物，应在随机临床试验中进一步评估。
