Role of ABCG2 expression driven by cisplatin in platinum-containing chemotherapy for gastric cancer

World J Gastroenterol. 2013 Oct 21;19(39):6630-6. doi: 10.3748/wjg.v19.i39.6630.

Abstract

Aim: To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer.

Methods: Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011. Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h. Polymerase chain reaction products were run on 2% agarose gels and analyzed under ultraviolet light after ethidium bromide staining. Increases in ABCG2 mRNA expression time were assessed after cancer cells were incubated with cisplatin, and were divided into terciles and compared in relation to clinical outcomes.

Results: Among groups classified by expression time of ABCG2 mRNA, no significant differences in baseline clinical characteristics and pathological findings were detected. The median overall time was 14.2 (95%CI: 9.7-18.6), 11.4 (95%CI: 6.3-16.5) and 8.1 (95%CI: 5.4-10.8) in patients with low, intermediate and high increases in ABCG2 mRNA expression times (P < 0.05), respectively. Median survival associated with performance status and tumor node metastasis (TNM) stage showed a similar trend, with longer survival and higher risk for mortality associated with lower performance status score and TNM stage. In a multivariate analysis for survival with Cox proportional-hazards model, increased ABCG2 mRNA expression time was an independent predictor for overall survival. Overall survival was longer with increased ABCG2 mRNA expression times ≤ 0.71 than increased ABCG2 mRNA expression times > 0.71, with a hazard ratio for death of 0.855 (95%CI: 0.615-0.962, P = 0.038).

Conclusion: Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients, and this may help modify the therapeutic strategies.

Keywords: ABCG2 mRNA expression; Cisplatin; Gastric cancer; Overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Case-Control Studies
  • Chi-Square Distribution
  • Cisplatin / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Proteins / drug effects*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Risk Factors
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Time Factors
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • RNA, Messenger
  • Cisplatin