Elevated Expression Of Dtymk Is Associated With Poor Prognosis In Patients With Non-Small Cell Lung Cancer
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2016)
摘要
Deoxythymidylate Kinase (DTYMK), a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of dTMP to produce dTDP in the presence of ATP and magnesium, has recently been considered to be associated with the progress of various human cancers. However, the clinical significance of DTYMK in Non-small cell lung cancer (NSCLC) remains unclear. In the present study, we performed immunohistochemistry analysis on human tissue microarray (TMA) to detect the DTYMK protein expression pattern, which was further validated by high-throughput sequencing data TCGA database at mRNA level. Immunohistochemistry analysis found that DTYMK protein expression in NSCLC tissues was significantly higher than those in normal lung tissues (P=0.000). Additionally, high DTYMK was dramatically associated with the advanced tumor status (P=0.000), enhanced nodal status (P=0.000) and high TNM stage (P=0.000). The mRNA expression in TCGA database showed that DTYMK was upregulated in NSCLC tissues with old age (P=0.018), smokers (P=0.017), and high TNM stage (P=0.005). Furthermore, Kaplan-Meier survival curves revealed that NSCLC patients with high DTYMK levels had shorter survival compared with those showing low DTYMK expression (P=0.012). The upregulation of DTYMK was an independent prognostic factor for NSCLC patients (HR: 0.472, 95% CI 0.251-0.887; P=0.020). In conclusion, our findings disclose that DTYMK may play an important role in tumor progression of NSCLC and high DTYMK may efficiently predict poor prognosis in NSCLC patients.
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关键词
Non-small cell lung cancer, deoxythymidylate kinase, clinicopathological feature, tumor promoter, prognosis
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