Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: A systematic review and meta-analysis

Liu, Qingyun; Yu, Zhengping; Xiang, Ying; Wu, Na; Wu, Long; Xu, Bin; Wang, Liang; Yang, Ping; Li, Yafei; Li, Bai

doi:10.3233/cbm-140432

Cited by 17 publications

(13 citation statements)

References 58 publications

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“…Despite major advances in therapeutic strategies, the prognosis for NSCLC patients remains poor; the 5-year survival rate is less than 15% 2 . A growing number of molecular alterations and specific gene expression signatures have been implicated in NSCLC carcinogenesis, including KRAS , EGFR mutations, EML4-ALK rearrangements, and VEGF and thymidylate synthase expression levels, among others 3–5 . However, the detailed molecular pathogenesis of NSCLC is far from fully understood.…”

Section: Introductionmentioning

confidence: 99%

Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

You

Liu

et al. 2017

Sci Rep

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Farnesoid X receptor (FXR), a nuclear receptor for maintaining bile acid homeostasis, has been recognized as a tumor suppressor in enterohepatic tissues. However, its expression and functional role in non-small cell lung cancer (NSCLC) remain unclear. We report that FXR is significantly increased in NSCLC and that it predicts poor clinical outcomes in NSCLC patients. FXR knockdown in NSCLC cells inhibited in vitro cell proliferation, blocked xenograft growth in nude mice, and delayed the G1/S transition of the cell cycle, whereas ectopic overexpression of FXR promoted NSCLC cell proliferation. Mechanistic analysis demonstrated that FXR could directly bind to an inverted repeat-0 sequence in the CCND1 promoter and activate its transcription. Cyclin D1 overexpression rescued NSCLC cells from the delayed G1/S transition and the impaired cell proliferation induced by FXR knockdown. Importantly, a positive correlation between the expression of FXR and cyclin D1 was confirmed in NSCLC samples, and patients with high expression of both FXR and cyclin D1 had the worst prognosis. In summary, our results suggest that FXR has oncogenic potential in NSCLC development, providing mechanistic insights that could be exploited for both prognostic and therapeutic purposes.

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Section: Introductionmentioning

confidence: 99%

Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

You

Liu

et al. 2017

Sci Rep

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“…In a meta‐analysis, Liu et al . reported that TS expression had prognostic value in NSCLC patients who received TS inhibitor treatment …”

Section: Introductionmentioning

confidence: 99%

Topoisomerase I expression is associated with prognosis in postoperative non‐small cell lung cancer patients

Zhang

et al. 2016

Thoracic Cancer

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BackgroundBiomarkers may help to improve non‐small cell lung cancer (NSCLC) prognosis. However, the prognostic effect of topoisomerase I (Topo I) on NSCLC is unknown. We evaluated the clinicopathologic and prognostic significance of tumor Topo I and thymidylate synthase (TS) protein expression in postoperative NSCLC patients.MethodsOne hundred and fifteen patients with postoperative NSCLC were enrolled. Topo I and TS protein were detected in removed tumors by immunohistochemistry. The correlations between Topo I/TS protein expression and clinicopathologic characters and outcomes of patients were analyzed.ResultsIncreased expression of Topo I was found in 57 (49.6%) tumors. The largest diameter of the tumor was significantly different between patients with high and low Topo I expression (P = 0.035). TS staining showed that 35 (30.4%) carcinomas were TS positive. The level of TS expression was correlated with tumor differentiation (P = 0.037). Patients with low Topo I expression had significantly longer overall survival (OS) than those with high expression (P = 0.004). The correlation between Topo I expression and OS was demonstrated among patients with squamous cell carcinoma (P = 0.030) and patients in pathological tumor node metastasis stage I (P = 0.027). Topo I expression was positively correlated with TS expression in tumor tissue (R = 0.251, P = 0.007).ConclusionsLow Topo I expression is an independent favorable prognostic factor for longer OS in postoperative NSCLC patients, especially in squamous cell carcinoma. There is a correlation between the expression of TS and Topo I in removed tumor tissue.

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“…More than 80% of lung cancer are non-small cell lung cancer (NSCLC) (2,3). In China, the incidence of lung cancer in the past few decades has doubled due to the aging population, smoking and decline in air quality (4).…”

Section: Introductionmentioning

confidence: 99%

Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

Tian

Liu²,

Pei

et al. 2016

Oncology Reports

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Abstract.To explore the potential therapeutic targets of early-stage non-small cell lung cancer (NSCLC), gene microarray analysis was conducted. The microarray data of NSCLC in stage IA, IB, IIA, and IIB (GSE50081), were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IB vs. IA, IIA vs. IB, IIB vs. IIA were screened out via R. ToppGene Suite was used to get the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs. The GeneCoDis3 database and Cytoscape software were used to construct the transcriptional regulatory network. In total, 25, 17 and 14 DEGs were identified in IB vs. IA, IIA vs. IB, IIB vs. IIA of NSCLC, respectively. Some GO terms and pathways (e.g., extracellular space, alveolar lamellar body, bioactivation via cytochrome P450 pathway) were found significantly enriched in DEGs. Genes S100P, ALOX15B, CCL11, NLRP2, SERPINA3, FoxO4 and hsa-miR-491 may play important roles in the development of early-stage NSCLC. Thus, by bioinformatics analysis the key genes and biological processes involving in the development of early-stage NSCLC could be established, providing more potential references for the therapeutic targets.

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Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: A systematic review and meta-analysis

Abstract: Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs. Prognostic value of TS protein expression needs further validation.

Cited by 17 publications

References 58 publications

Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

Topoisomerase I expression is associated with prognosis in postoperative non‐small cell lung cancer patients

Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

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