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. 2018 Jul;9(1):21-29.
doi: 10.3892/mco.2018.1619. Epub 2018 May 4.

The relationship between the expression of thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase, excision repair cross-complementation group 1 and class III β-tubulin, and the therapeutic effect of S-1 or carboplatin plus paclitaxel in non-small-cell lung cancer

Katsuhiro Okuda  1 , Tsutomu Tatematsu  1 , Motoki Yano  2 , Katsumi Nakamae  3 , Takeshi Yamada  4 , Toshio Kasugai  5 , Tsutomu Nishida  6 , Masaaki Sano  7 , Satoru Moriyama  1 , Hiroshi Haneda  1 , Osamu Kawano  1 , Tadashi Sakane  1 , Risa Oda  1 , Takuya Watanabe  1 , Ryoichi Nakanishi  1
Affiliations

The relationship between the expression of thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase, excision repair cross-complementation group 1 and class III β-tubulin, and the therapeutic effect of S-1 or carboplatin plus paclitaxel in non-small-cell lung cancer

Katsuhiro Okuda et al. Mol Clin Oncol. 2018 Jul.

Abstract

Previous studies have reported that the expressions of specific proteins may predict the efficacy of chemotherapy agents for non-small cell lung cancer (NSCLC) patients. The present study evaluated the expression of proteins hypothesized to be associated with the effect of chemotherapeutic agents in 38 NSCLC patients with pathological stage II and IIIA. The subjects received carboplatin plus paclitaxel (CP) or S-1 as adjuvant chemotherapy following complete resection. The protein expressions evaluated were those of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phsphoribosyltransferase (OPRT), which were suspected to be associated with the effect of S-1 agents, excision repair cross-complementation group 1 (ERCC1), which was suspected to be associated with the effect of platinum-based agents, and class III β-tubulin (TUBB3), which was suspected to be associated with the effect of taxane-based agents. The positive rate of TS was 55.3% (n=21/38), DPD was 57.9% (n=22/38), OPRT was 42.1% (n=16/38), ERCC1 was 47.4% (n=18/38) and TUBB3 was 44.7% (n=17/38). Among the patients who received S-1 adjuvant chemotherapy, TS-negative cases demonstrated a significantly better disease-free survival than positive cases. Thus, TS protein expression may have been a factor that predicted the effect of S-1 agent as adjuvant chemotherapy.

Keywords: adjuvant chemotherapy; class III β-tubulin; dihydropyrimidine dehydrogenase; excision repair cross-complementation group 1; non-small cell lung cancer; orotate phsphoribosyltransferase; protein expression; thymidylate synthase.

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Figures

Figure 1.
Figure 1.
Representative positive and negative cases of each immunohistochemistry result observed (magnification, ×200). (A) TS positive case. (B) TS negative case. (C) DPD positive case. (D) DPD negative case. (E) OPRT positive case. (F) OPRT negative case. (G) ERCC1 positive case. (H) ERCC1 negative case. (I) TUBB3 positive case. (J) TUBB3 negative case. TS, thymidylate synthase; DPD, dihydropyrimidine dehydrogenase; ORPT, orotate phsphoribosyltransferase; ERCC1, excision repair cross-complementation group 1; TUBB3, class III β-tubulin.
Figure 2.
Figure 2.
Kaplan-Meier analyses. (A) The 5-year overall survival of the 38 patients who received carboplatin plus paclitaxel or S-1 adjuvant chemotherapy. (B) The 5-year disease-free survival of the 38 patients who received carboplatin plus paclitaxel or S-1 adjuvant chemotherapy. (C) The overall survival divided by carboplatin plus paclitaxel or S-1 adjuvant chemotherapy. (D) The disease-free survival divided by carboplatin plus paclitaxel or S-1 adjuvant chemotherapy.
Figure 3.
Figure 3.
Kaplan-Meier analyses. (A) The overall survival of the 38 patients associated withthe protein expression of TS. (B) The disease-free survival of the 38 patients associated with the protein expression of TS. (C) The overall survival of the 19 patients who received S-1 adjuvant chemotherapy, associated with the protein expression of TS. (D) The disease-free survival of the 19 patients who received S-1 adjuvant chemotherapy, associated with the protein expression of TS. TS, thymidylate synthase.
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