Genotyping May Lead To Personalized Lung Cancer Therapy

MedicalResearch.com Interview with:
Keiji Tanimoto, D.D.S., Ph.D

Assistant Professor
Research Institute for Radiation Biology and Medicine
Hiroshima University
Hiroshima Japan

Medical Research: What is the background for this study?

Dr. Tanimoto: Hypoxia-inducible factor-2α (HIF-2αor EPAS1) is important for cancer progression, and its overexpression is considered a putative biomarker for poor prognosis in patients with lung cancer. However, molecular mechanisms underlying EPAS1 overexpression are not fully understood. Recently, several SNPs of EPAS1 have been reported to be associated with the development of various diseases including cancer.

Therefore, we focused on SNPs within EPAS1, and examined the roles of these SNPs in regulation of EPAS1 gene expression and the association of these SNPs with prognosis of non-small cell lung cancer (NSCLC) patients by bioinformatics analyses.

Medical Research: What are the main findings?

Dr. Tanimoto:

  • The SNP within the EPAS1 intron 1 region (rs13419896) may affect EPAS1 gene and protein expression;
  • The fragment with A allele of the SNP showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun;
  • The median survival time of NSCLC patients with at least one A allele of rs13419896 was significantly shorter than that with the G/G homozygote (28.0 vs. 52.5 months, P = 0.047, log-rank test);
  • The possession of A allele of rs13419896, along with clinical stage, was an independent variable for risk estimation of overall survival for NSCLC patients [hazard ratio (HR) = 2.31, 95% CI = 1.14-4.81, P = 0.021], after adjustment for age, gender, stage, histology, tumor size, and differentiation.

Medical Research: What should clinicians and patients take away from your report?

Dr. Tanimoto: We found that nucleotide difference at the rs13419896 SNP may affect EPAS1 gene and protein expression and that the A allele of EPAS1 SNP is associated with poorer prognosis of NSCLC patients. On confirmation of our observation in the future, genotyping for the EPAS1 SNP may become a clinically useful tool in personalized health examinations and cancer therapy.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Tanimoto: To establish the EPAS1 SNP as a useful clinical prognostic marker and to further clarify their molecular mechanisms, larger scale clinicopathological studies of lung cancer and/or other types of cancer will provide additional insights into these aspects.

Citation:

Andika C. Putra, Hidetaka Eguchi, Kian Leong Lee, Yuko Yamane, Ewita Gustine, Takeshi Isobe, Masahiko Nishiyama, Keiko Hiyama, Lorenz Poellinger, Keiji Tanimoto. The A Allele at rs13419896 of EPAS1 Is Associated with Enhanced Expression and Poor Prognosis for Non-Small Cell Lung Cancer. PLOS ONE, 2015; 10 (8): e0134496 DOI:1371/journal.pone.0134496

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Keiji Tanimoto, D.D.S., Ph.D (2015). Genotyping May Lead To Personalized Lung Cancer Therapy