Loeser Heike, Schallenberg Simon, von Winterfeld Moritz, Tharun Lars, Alakus Hakan, Hölscher Arnulf, Bollschweiler Elfriede, Buettner Reinhard, Zander Thomas, Quaas Alexander
Institute of Pathology, University of Cologne, Cologne, Germany.
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
Oncotarget. 2017 Dec 11;8(70):115179-115189. doi: 10.18632/oncotarget.23112. eCollection 2017 Dec 29.
Esophageal adenocarcinomas show an increasing incidence in the Western world and their overall survival remains low. Microtubules are multifunctional cytoskeletal proteins involved in crucial cellular roles, including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Microtubulus-TUBB3 was found overexpressed in several carcinomas suggesting a significant role in cancer development. High levels of TUBB3 expression were also described to be associated with poor clinical outcome in various cancers. It was shown that overexpression of TUBB3 could be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types.
There is a statistically significant association between high TUBB3 protein and TUBB3 mRNA expression and shortened survival (p<0,0001). Prognostic impact of TUBB3 expression is seen in patients with and without multimodal treatment. Multivariate analysis revealed a strong TUBB3 expression to be an independent prognosis factor. Validation of protein expression by mRNA in situ hybridization underlines the credibility of the immunohistochemical results.
Our study emphasized the significant importance of TUBB3 in esophageal adenocarcinoma. TUBB3 serves as an independent prognostic marker and may be a valuable biomarker for routine application in esophageal adenocarcinoma especially to address the need for adjuvant treatment in individuals following neoadjuvant therapy and surgery. Future prospective studies are needed which include the results of TUBB3 in preoperative biopsy material to proof the prognostic impact of TUBB3.
280 esophageal adenocarcinomas that underwent primary surgical resection or resection after neoadjuvant therapy were analyzed by mRNA-in-situ-hybridization (RNAscope) and by immunohistochemistry (TUBB3 rabbit monoclonal antibody; Epitomics).
在西方世界，食管腺癌的发病率呈上升趋势，但其总体生存率仍然很低。微管是多功能细胞骨架蛋白，参与关键的细胞功能，包括维持细胞形状、细胞内运输、减数分裂和有丝分裂。在几种癌症中发现微管蛋白-TUBB3过表达，提示其在癌症发展中起重要作用。在各种癌症中，高水平的TUBB3表达也与不良临床结局相关。研究表明，在几种癌症类型中，TUBB3的过表达可能与紫杉烷类靶向抗癌药物的疗效降低有关。
TUBB3蛋白和TUBB3 mRNA高表达与生存期缩短之间存在统计学上的显著关联（p<0.0001）。在接受和未接受多模式治疗的患者中均可见TUBB3表达的预后影响。多变量分析显示，TUBB3高表达是一个独立的预后因素。通过mRNA原位杂交验证蛋白表达，强调了免疫组化结果的可信度。
我们的研究强调了TUBB3在食管腺癌中的重要意义。TUBB3作为一个独立的预后标志物，可能是食管腺癌常规应用中有价值的生物标志物，特别是满足新辅助治疗和手术后个体辅助治疗的需求。未来需要进行前瞻性研究，包括术前活检材料中TUBB3的结果，以证实TUBB3的预后影响。
对280例接受初次手术切除或新辅助治疗后切除的食管腺癌进行mRNA原位杂交（RNAscope）和免疫组化分析（TUBB3兔单克隆抗体；Epitomics）。
