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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Cell Transformation, Neoplastic
  • DNA Repair / genetics*
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism*
  • Thymoma / drug therapy
  • Thymoma / enzymology
  • Thymoma / genetics
  • Thymoma / pathology*
  • Thymus Neoplasms / drug therapy
  • Thymus Neoplasms / enzymology
  • Thymus Neoplasms / genetics
  • Thymus Neoplasms / pathology*
  • Young Adult
  • ral Guanine Nucleotide Exchange Factor / genetics
  • ral Guanine Nucleotide Exchange Factor / metabolism

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger
  • Rgl3 protein, human
  • ral Guanine Nucleotide Exchange Factor
  • Thymidylate Synthase
  • TOR Serine-Threonine Kinases
  • ERCC1 protein, human
  • Endonucleases
  • DNA Topoisomerases, Type II
  • TOP2A protein, human