胸腺瘤中胸苷酸合成酶和 DNA 修复基因的信使 RNA 和蛋白表达。

Messenger RNA and protein expression of thymidylate synthase and DNA repair genes in thymic tumors.

机构信息

Division of Pathology, Department of Clinical & Biological Sciences, University of Torino at St Luigi Hospital, Turin, Italy.

出版信息

Lung Cancer. 2013 Mar;79(3):228-35. doi: 10.1016/j.lungcan.2012.12.003. Epub 2012 Dec 28.

DOI:10.1016/j.lungcan.2012.12.003

PMID:23276504

Abstract

BACKGROUND

Thymic epithelial tumors include several entities with different biologic behavior. Chemotherapy is indicated in advanced disease, but limited data exist on gene expression correlation with the response to chemotherapeutic agents.

PATIENTS AND METHODS

A series of 69 thymic neoplasms (7 A-, 6 AB-, 6 B1-, 10 B2-, 14 B3-thymomas, 22 carcinomas and 4 combined tumors) was collected to assess gene expression of thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), ribonucleotide reductase subunit 1 (RRM1), topoisomerase 2α (TOP2A) and mTOR.

RESULTS

A strong linear correlation between TS gene and protein expression was observed (P<0.0001, R=0.40). TS expression was significantly lower in pure A-thymomas and thymic carcinomas (P<0.0001) and progressively decreasing from B1-type to thymic carcinomas (B1>B2>B3>C; P<0.0001). RRM1 and TOP2A mRNA expression levels were significantly correlated with TS levels (both P=0.03) with a similar trend of expression among histotypes. RRM1 and TOP2A high levels were significantly correlated with high TS (P=0.03) and low tumor stages (I-II) (P<0.0001 and P<0.01, respectively). No relevant changes of ERCC1 and mTOR were detected.

CONCLUSIONS

Low TS and, to a minor extent, RRM1 and TOP2A expression were detected in aggressive thymic tumors. These findings should be prospectively considered in selecting the most appropriate chemotherapy.

摘要

背景

胸腺瘤包括多种具有不同生物学行为的实体瘤。化疗适用于晚期疾病，但关于基因表达与化疗药物反应相关性的有限数据。

患者和方法

收集了一系列 69 例胸腺瘤（7 例 A 型、6 例 AB 型、6 例 B1 型、10 例 B2 型、14 例 B3 型胸腺瘤、22 例癌和 4 例联合肿瘤），以评估胸苷酸合成酶（TS）、切除修复交叉互补基因 1（ERCC1）、核糖核苷酸还原酶亚单位 1（RRM1）、拓扑异构酶 2α（TOP2A）和 mTOR 的基因表达。

结果

TS 基因和蛋白表达之间存在很强的线性相关性（P<0.0001，R=0.40）。纯 A 型胸腺瘤和胸腺癌的 TS 表达显著降低（P<0.0001），从 B1 型到胸腺癌呈逐渐下降趋势（B1>B2>B3>C；P<0.0001）。RRM1 和 TOP2A mRNA 表达水平与 TS 水平显著相关（均 P=0.03），不同组织学类型的表达趋势相似。RRM1 和 TOP2A 高水平与高 TS（P=0.03）和低肿瘤分期（I-II）显著相关（分别为 P<0.0001 和 P<0.01）。未检测到 ERCC1 和 mTOR 的相关变化。