Deciphering Clinicoradiologic Phenotype for Thymidylate Synthase Expression Status in Patients with Advanced Lung Adenocarcinoma Using a Radiomics Approach.
In this study, we investigated whether AEG-1 expression level correlated with that of thymidylate synthase (TS), as higher TS expression is known to be associated with the resistance to pemetrexed chemotherapy in patients with advanced lung adenocarcinoma.
However, the H-score of thymidylate synthase was not associated with the response to pemetrexed therapy in patients with different molecular subtypes of lung adenocarcinoma.
Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia.
Downregulation of TYMS protein and mRNA expression, reduced TYMS activity, and suppressed E2F1 expression were demonstrated in lung adenocarcinoma with ATO.
The median thymidylate synthase RNA level from 85 EML4-ALK+ cancers was significantly lower compared with that of EML4-ALK-negative lung adenocarcinomas (2.02 versus 3.29, respectively, p<0.001).
Our results indicated that SUV(max) by ¹⁸F-FDG uptake may be an alternative biomarker for predicting TS expression in patients with primary lung adenocarcinoma, high-grade NE tumor, thymoma and MPM.
We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung.
TYMS copy numbers in lung adenocarcinoma cell lines were significantly lower than in squamous cell carcinoma (p=0.0105), and a significant correlation was found between the TYMS copy number and the 50% inhibitory concentration value for pemetrexed in all 17 lung cancer cell lines tested (r=0.6814, p=0.0026).
Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma.
We measured TS expression in surgically resected pulmonary tumors, comparing HGNE carcinomas of the lung (13 large-cell neuroendocrine carcinomas, 8 small-cell lung carcinomas) with squamous cell carcinoma and adenocarcinoma of the lung using laser-capture microdissection for tissue isolation, real-time polymerase chain reaction (PCR), and immunohistochemistry.
The expression levels of TS mRNA were measured in 47 lung adenocarcinoma tissues using the Taq-Man real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method and examined the clinicopathologic significance of TS expression.