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Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients.

Zhao HY, Ma GW, Zou BY, Li M, Lin SX, Zhao LP, Guo Y, Huang Y, Tian Y, Xie D, Zhang L - Onco Targets Ther (2014)

Bottom Line: Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003).Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005).However, the OS was not significantly correlated with OPRT or TP protein expression.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

ABSTRACT
The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102 carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003). Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005). However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker to predict the postoperative OS in NSCLC patients.

No MeSH data available.


Related in: MedlinePlus

(A) Kaplan–Meier plot of OS in TS negative and positive groups; (B) adenocarcinoma patients; (C) patients under 60 years old; (D) patients with pT1/T2; (E) patients with pN0/N1; (F) patients with stage II/III; (G) patients with surgery plus chemotherapy and/or radiation treatment.Abbreviations: C, chemotherapy; OS, overall survival; pN, pathologic nodal; pT, pathologic tumor size; R, radiotherapy; S, surgery; TS, thymidylate synthase; y, years.
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f2-ott-7-1301: (A) Kaplan–Meier plot of OS in TS negative and positive groups; (B) adenocarcinoma patients; (C) patients under 60 years old; (D) patients with pT1/T2; (E) patients with pN0/N1; (F) patients with stage II/III; (G) patients with surgery plus chemotherapy and/or radiation treatment.Abbreviations: C, chemotherapy; OS, overall survival; pN, pathologic nodal; pT, pathologic tumor size; R, radiotherapy; S, surgery; TS, thymidylate synthase; y, years.

Mentions: In the whole cohort, the 5-year and 10-year survival rates were 42% and 31%, respectively. Using univariate analysis, the TS-positive patients had a significantly higher OS rate than did the TS-negative patients (P=0.003) (Figure 2A and Table 2). Stratified analysis revealed that the positive correlation between TS expression and OS was found in ADC (P=0.005) (Figure 2B) but not in squamous cell carcinoma and adenosquamous cell carcinoma. Furthermore, similar positive correlation was also found using the following parameters: patients <60 years (P=0.028) (Figure 2C), pathologic tumor size (pT)1/T2 (P<0.001) (Figure 2D), pN0/N1 (P<0.010) (Figure 2E), stage II/III (P=0.032) (Figure 2F), and surgery plus chemotherapy and/or radiation (P=0.002) (Figure 2G). Results from hazard ratios (HRs) showed that the TS-negative group had higher risk of death, in the whole group and in subgroups, such as ADC, patients <60 years, pT1/T2, pN0/N1, and stage II/III, surgery plus chemotherapy and/or radiation (Table 3). However, neither OPRT expression nor TP expression was significantly correlated to OS, in the whole cohort and subgroups. In addition, Kaplan–Meier analysis demonstrated that some clinicopathologic prognostic parameters, such as tumor pN status (P<0.001) and clinical stage (P<0.001), were related to patient survival, but no significant correlation was found between survival and other clinicopathologic parameters (data not shown).


Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients.

Zhao HY, Ma GW, Zou BY, Li M, Lin SX, Zhao LP, Guo Y, Huang Y, Tian Y, Xie D, Zhang L - Onco Targets Ther (2014)

(A) Kaplan–Meier plot of OS in TS negative and positive groups; (B) adenocarcinoma patients; (C) patients under 60 years old; (D) patients with pT1/T2; (E) patients with pN0/N1; (F) patients with stage II/III; (G) patients with surgery plus chemotherapy and/or radiation treatment.Abbreviations: C, chemotherapy; OS, overall survival; pN, pathologic nodal; pT, pathologic tumor size; R, radiotherapy; S, surgery; TS, thymidylate synthase; y, years.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4109640&req=5

f2-ott-7-1301: (A) Kaplan–Meier plot of OS in TS negative and positive groups; (B) adenocarcinoma patients; (C) patients under 60 years old; (D) patients with pT1/T2; (E) patients with pN0/N1; (F) patients with stage II/III; (G) patients with surgery plus chemotherapy and/or radiation treatment.Abbreviations: C, chemotherapy; OS, overall survival; pN, pathologic nodal; pT, pathologic tumor size; R, radiotherapy; S, surgery; TS, thymidylate synthase; y, years.
Mentions: In the whole cohort, the 5-year and 10-year survival rates were 42% and 31%, respectively. Using univariate analysis, the TS-positive patients had a significantly higher OS rate than did the TS-negative patients (P=0.003) (Figure 2A and Table 2). Stratified analysis revealed that the positive correlation between TS expression and OS was found in ADC (P=0.005) (Figure 2B) but not in squamous cell carcinoma and adenosquamous cell carcinoma. Furthermore, similar positive correlation was also found using the following parameters: patients <60 years (P=0.028) (Figure 2C), pathologic tumor size (pT)1/T2 (P<0.001) (Figure 2D), pN0/N1 (P<0.010) (Figure 2E), stage II/III (P=0.032) (Figure 2F), and surgery plus chemotherapy and/or radiation (P=0.002) (Figure 2G). Results from hazard ratios (HRs) showed that the TS-negative group had higher risk of death, in the whole group and in subgroups, such as ADC, patients <60 years, pT1/T2, pN0/N1, and stage II/III, surgery plus chemotherapy and/or radiation (Table 3). However, neither OPRT expression nor TP expression was significantly correlated to OS, in the whole cohort and subgroups. In addition, Kaplan–Meier analysis demonstrated that some clinicopathologic prognostic parameters, such as tumor pN status (P<0.001) and clinical stage (P<0.001), were related to patient survival, but no significant correlation was found between survival and other clinicopathologic parameters (data not shown).

Bottom Line: Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003).Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005).However, the OS was not significantly correlated with OPRT or TP protein expression.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

ABSTRACT
The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102 carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003). Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005). However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker to predict the postoperative OS in NSCLC patients.

No MeSH data available.


Related in: MedlinePlus