Search

Background and purpose: The expression of programmed death ligand-1 (PD-L1) in lung cancer not only is the most important biomarker for predicting the efficacy of programmed death-1 (PD-1)/PD-L1 inhibitors, but also may affect the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeted therapy. However, there are currently few reports in the relevant literature on whether the expression of PD-L1 in lung cancer can affect the efficacy of chemotherapy in patients with lung adenocarcinoma. This study mainly explored the effect of PD-L1 expression in lung adenocarcinoma on the efficacy of pemetrexed-based chemotherapy and its underlying mechanism. Methods: From Oct. 2015 to Dec. 2018, 185 eligible lung adenocarcinoma patients treated in Department of Pathology, The General Hospital of Western Theater Command PLA were enrolled. The expressions of PD-L1 and thymidylate synthase (TS), a molecule predicting the efficacy of pemetrexed-based chemotherapy, were detected by immunohistochemistry. The survival curve of patients was drawn by Kaplan-Meier method. The log-rank test and COX regression model were used to analyze the clinicopathological factors affecting the patients’ progression-free survival (PFS) and overall survival (OS). The log-rank test was used to analyze the effects of PD-L1 and TS expressions on the patients’ PFS and OS. Spearman rank correlation test was used to analyze the correlation between PD-L1 expression and TS expression in lung cancer tissues. Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) were used to detect the protein and mRNA expressions of PD-L1 and TS in 6 types of lung adenocarcinoma cell lines. The Pearson correlation test was used to analyze the correlation between PD-L1 and TS at protein expression level and mRNA expression level. Results: Among 51 patients with advanced lung adenocarcinoma who received pemetrexed-based chemotherapy as first-line treatment, the objective response rate (ORR) of the PD-L1 positive group was 20.0%, and the disease control rate (DCR) was 60.0%. There was no significant difference compared with the PD-L1 negative group (ORR: 20.0% vs 35.5%, χ 2 =1.404, P=0.236; DCR: 60.0% vs 80.6%, χ 2 =2.602, P=0.107). The median PFS (mPFS) of patients with negative expression of PD-L1 was significantly better than that of patients with positive expression of PD-L1 (mPFS: 5.6 months vs 4.1 months, log-rank=5.406, P=0.020), and there was no significant difference in median OS (mOS) between them (mOS: 15.9 months vs 12.7 months, log-rank=0.525, P=0.469). Univariate analysis found that the positive expressions of PD-L1 and TS were risk factors for PFS ［PD-L1 negative vs positive: HR=2.002 (1.100-3.645), P=0.023; TS negative vs positive: HR=2.205 (1.367-4.587), P=0.003］. Multivariate analysis found that TS positive expression was an independent risk factor for PFS ［TS negative vs positive: HR=3.245 (1.091-9.652), P=0.034］. Among the 51 patients with advanced lung adenocarcinoma who received pemetrexed-based chemotherapy as the first-line treatment, the expression of PD-L1 in cancer tissues was significantly positively correlated with the expression of TS (r s =0.691, P

Objective: To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance., Methods: Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100., Results: The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 ( P >0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%., Conclusions: TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.

Objective: To investigate epidermal growth factor receptor (EGFR) and thymidylate synthase (TS) expression in primary liver cancer, and analyze its clinicopathological features and prognostic significance. Methods: Immunohistochemistry was performed using EnVision method to detect EGFR and TS expression in 41 cases of liver cancer. Correlation coefficient between EGFR and TS was calculated by Spearman method. Fisher's exact probability method or χ (2) test was used to analyze the clinicopathological features of EGFR and TS. Kaplan-Meier method was used to calculate the survival rate of patients in conjunction with the log-rank test.COX proportional hazard regression model was used to analyze the prognostic factors of patients. ROC curve was used to analyze the predictive accuracy of EGFR and TS for prognosis. Results: The positive rates of EGFR and TS in liver cancer tissues were 34.15% and 39.02%, respectively. There was a positive correlation between EGFR and TS expressions, and the difference was statistically significant ( P < 0.05). EGFR was associated with tumor size and tissue differentiation ( P < 0.05) in HCC patients, whereas TS was associated with tissue differentiation ( P < 0.05). There was no significant difference in prognostic effect of EGFR on survival rate ( P > 0.05). TS prognostic effect on survival rate was statistically significant ( P < 0.05). HR of EGFR was 0.210 with 95% CI , 0.052-0.852, P = 0.029; indicating that the risk of death in patients with negative EGFR was 0.210 times higher than that in patients with positive EGFR. HR of TS was 2.496, with 95% CI , 1.325-4.701, P = 0.005, indicating that the risk of death increased by 2.496 times with the same level of EGFR. The area under the EGFR curve was 0.553 and its approximate reference confidence interval was 95% (0.355, 0.751), indicating that EGFR was a risk factor for death and the area under the TS curve was 0.695, and its approximate reference confidence interval was 95% (0.513, 0.878), indicating that TS was a risk factor for death. Conclusion: EGFR and TS were equally expressed in primary liver cancer, and EGFR and TS expressions were positively correlated. EGFR and TS had an effect on the degree of tissue differentiation in patients with liver cancer. EGFR and TS were risk factors for prognosis, and TS may assist EGFR.

Objective: To establish human choriocarcinoma JeG-3 cell line resistant to floxuridine (FUDR) and describe the characteristics of this FUDR-resistant subline. The thymidylate synthase (TS) expression level in FUDR-resistant subline was also discussed., Methods: The FUDR-resistant sub-line JeG-3/FUDRA was established by intermitted exposure to grads increased FUDR. Reversed microscope was used to observe the morphological changes in FUDR-resistant sub-line. Population doubling time was calculated and compared based on the growth curve of these two cell lines, cell cycles and chromosomal ploidy were assayed with flow cytometry methods. The chemo-luminescence assay was used to detect the hormone secretion by two kinds of cell lines. The resistant index (RI) was measured by cell counting kit-8 (CCK-8) assay. Quantitative RT-PCR was used to detect the mRNA expression level of TS and we also detected the TS mRNA expression level in different doses exposed subline., Results: The RI of JeG-3/FUDRA was 31.62. Compared with the JeG-3 cell, the FUDR-resistant cell line had gross changes in morphological, cell growth, cell cycles and chromosomal numbers. The ability of human chorionic gonadotrop (hCG) and progesterone secretion was lower in JeG-3/FUDRA subline. The trend of TS mRNA expression was: while exposed to low concentration of FUDR, the TS mRNA expression level was downregulated, then followed the increasing dose of the drug, the expression level of TS mRNA ascended gradually. When the terminal concentration was reached, the expression level of TS mRNA in JeG-3/FUDRA subline was higher than that of JeG-3 cell line (P < 0.05)., Conclusions: We established the FUDR-resistant subline of JeG-3 successfully. The TS mRNA expression level is stage-related to the different concentration and different phase in FUDR exposure. Our data suggested that TS mRNA expression level may not be used as a biomarker to predict the chemosensitivity in FUDR-based chemotherapy.