Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 25;12(1):19.
doi: 10.1007/s12672-021-00413-w.

Intratumoral gene expression of dihydrofolate reductase and folylpoly-c-glutamate synthetase affects the sensitivity to 5-fluorouracil in non-small cell lung cancer

Kayo Sakon  1 , Masato Sasaki  2 , Kaede Tanaka  2 , Tae Mizunaga  2 , Keita Yano  2 , Yuuko Kawamura  2 , Akitoshi Okada  2 , Takeshi Ikeda  3 , Sawaka Tanabe  2 , Atsushi Takamori  2 , Narihisa Yamada  2 , Kouichi Morioka  2 , Takaaki Koshiji  2
Affiliations

Intratumoral gene expression of dihydrofolate reductase and folylpoly-c-glutamate synthetase affects the sensitivity to 5-fluorouracil in non-small cell lung cancer

Kayo Sakon et al. Discov Oncol. .

Abstract

Background: Various factors related to the sensitivity of non-small cell lung carcinoma (NSCLC) to 5-fluorouracil (5-FU) have been reported, and some of them have been clinically applied. In this single-institutional prospective analysis, the mRNA expression level of five folic acid-associated enzymes was evaluated in surgical specimens of NSCLC. We investigated the correlation between the antitumor effect of 5-FU in NSCLC using an anticancer drug sensitivity test and the gene expression levels of five enzymes.

Materials and methods: Forty patients who underwent surgery for NSCLC were enrolled, and the antitumor effect was measured using an in vitro anticancer drug sensitivity test (histoculture drug response assay) using freshly resected specimens. In the same sample, the mRNA expression levels of five enzymes involved in the sensitivity to 5-FU were measured in the tumor using real-time PCR. The expression levels and the result of the sensitivity test were compared.

Results: No correlation was found between dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), or DPD/OPRT expression and the antitumor effects of 5-FU. On the other hand, a correlation was found between thymidylate synthase (TS), folylpoly-c-glutamate synthetase (FPGS), and dihydrofolate reductase (DHFR) expression and 5-FU sensitivity.

Conclusion: Expression of FPGS and DHFR may be useful for predicting the efficacy of 5-FU-based chemotherapy for NSCLC.

Keywords: Dihydropyrimidine dehydrogenase; Histoculture drug response assay; Orotate phosphoribosyltransferase; Reverse-transcriptase polymerase chain reaction; Thymidylate synthase.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
No significant correlation was found between expression of DPD (a), OPRT (b), and DPD/OPRT (c) and the percent inhibition with 5-FU using the HDRA method
Fig. 2
Fig. 2
A significant correlation was found between expression of TS (a), DHFR (b), and FPGS (c) and the percent inhibition with 5-FU using the HDRA method
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Arkenau HT, Bermann A, Rettig K, Strohmeyer G, Porschen R. 5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer; long-term follow-up results of the adjCCA-01 trials. Ann Oncol. 2003;14:395–399. doi: 10.1093/annonc/mdg100. - DOI - PubMed
    1. Takeda K. Clinical development of S-1 for non-small cell lung cancer: a Japanese perspective. Ther Adv Med Oncol. 2013;5(5):301–311. doi: 10.1177/1758834013500702. - DOI - PMC - PubMed
    1. Yoshioka H, Okamoto I, Morita S, et al. Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study. Ann Oncol. 2013;24(5):1326–1331. doi: 10.1093/annonc/mds629. - DOI - PubMed
    1. Kato H, Ichinose Y, Ohta M, Hata E. A Randomized Trial of Adjuvant Chemotherapy with Uracil–Tegafur for Adenocarcinoma of the Lung. N Engl J Med. 2004;350:1713–1721. doi: 10.1056/NEJMoa032792. - DOI - PubMed
    1. Ichikawa W, Uetake H, Shirota Y, et al. Both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Br J Cancer. 2003;89:1486–1492. doi: 10.1038/sj.bjc.6601335. - DOI - PMC - PubMed

LinkOut - more resources