Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine

Wang, Shalong; Yuan, Long

doi:10.5582/bst.2016.01078

Cited by 9 publications

(9 citation statements)

References 87 publications

(76 reference statements)

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“…It negatively regulates intracellular levels of phosiphatidylinositol-3,4,5-trisphosphate in cells and AKT/PKB signaling pathway, suppressing cellular functional activities [ 25 ]. Actually, emerging evidence has substantiated that PTEN could be targeted and regulated by miR-130a and miR-107 to influence cancerous cellular activities [ 26 , 27 ]. Nonetheless, there are fewer studies on the targeted relationships between miR-130a/miR-107 and PTEN in GC.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric Cancer by Sponging miR-130a/miR-107 and Modulating PTEN

Liu

et al. 2018

Cancer Res Treat

107

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PurposeThis study aimed to probe into the associations among circular RNA ZFR (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory mechanism of circ-ZFR‒miR-130a/miR-107‒PTEN axis in gastric cancer (GC).Materials and MethodsGSE89143 microarray data used in the study were acquired from publicly available Gene Expression Omnibus database to identify differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR, miR-130a, miR-107, and PTEN were examined by real-time reverse transcription polymerase chain reaction, while PTEN protein expression was measured by western blot. The variation of GC cell proliferation and apoptosis was confirmed by cell counting kit-8 assay and flow cytometry analysis. The targeted relationships among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics analysis and demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impact of ZFR on gastric tumor was further verified in xenograft mice model experiment.ResultsCirc-ZFR and PTEN were low-expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and cells. There existed targeted relationships and interactions between miR-130a/miR-107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein expression in vivo.ConclusionCirc-ZFR restrained GC cell proliferation, induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and regulating PTEN.

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Section: Discussionmentioning

confidence: 99%

Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric Cancer by Sponging miR-130a/miR-107 and Modulating PTEN

Liu

et al. 2018

Cancer Res Treat

107

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“…Most of the GC patients are diagnosed in an advanced stage and the survival rates of them are relatively low, therefore, promising prognostic biomarkers that enable to identify the patients who could obviously benefit from chemotherapy and predict survival of them are crucial [ 14 , 15 ]. In this study, we found that evaluated FPR was significantly associated with T3-4 invasion, node metastasis and larger tumor size and was superior to other biomarkers to independently predict poor survival both within stage II-III, II and III subgroups; moreover, clinical outcome of III stage patients with low FPR appeared to obviously benefit from adjuvant chemotherapy in comparison with high FPR stage III patients, and the biomarker could improve the predicted efficacy of nomogram for stage II-III GC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of a novel FPR biomarker in patients with surgical stage II and III gastric cancer

Zhang

Liao

et al. 2017

Oncotarget

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BackgroundInflammation and nutrition are two main causes contributing to progression of gastric cancer (GC), and inflammatory biomarker may be presented as its valuable prognostic factor. Thus, this study was carried out to investigate the prognostic significance of preoperative circulating albumin/fibrinogen ratio (AFR), fibrinogen/pre-Albumin ratio (FPR), fibrinogen (Fib), albumin (Alb) and pre-Albumin (pAlb) in surgical GC.Materials and MethodsThree hundred and sixty surgical stage II and III GC patients from June 2011 to December 2013 were enrolled in this retrospective study. X-tile software, Kaplan–Meier curve and Cox regression model were used to evaluate the prognostic role of them. A predictive nomogram was established to predict prognosis of overall survival (OS), and its accuracy was assessed by concordance index (c-index).ResultsDecreased Alb, pAlb, AFR and elevated FPR were significantly associated with shorter OS. FPR was identified as the most effective prognostic factor to predict 3-year’s OS by time-dependent ROC analysis. A long survival was observed in patients with low level of FPR and the prognosis of stage III FPR-low GC patients undergoing chemotherapy was significantly superior to the patients without the treatment (P=0.002). However, no difference of survival was examined in stage II subgroups stratified by FPR and high FRP of stage III patients with or not the treatment of chemotherapy. C-index of nomogram containing FPR (c-index=0.756) was high in comparison with the nomogram without FPR (c-index =0.748).ConclusionPreoperative FPR might be a feasible prognostic biomarker in surgical stage II and III GC and it could precisely distinguish stage III patients who appeared to obviously benefit from adjuvant chemotherapy. Meanwhile established nomogram based on clinical parameters and FPR could improve its predictive efficacy.

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“…The expression status of USP20 and Claspin was scored using a 4-point scale (0–4) based on the amount of positive cells and intensity of the staining under 5 random high-power fields. Score for percentage: <5% (0), 5–25% (1), 25–50% (2), 50–75% (3) and >75% (4); for intensity: no staining (0), light brown (1), brown (2) and dark brown (3). The final score of each specimen was calculated by multiplying staining intensity score with score of stained cells, score of ≤2, 3–4, 6–8 and 9–12 were defined as negative (−), weak (+), moderate (++) and strong (+++), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Radical gastrectomy offers the best opportunity for curative therapy, while most patients are diagnosed as advanced and unresectable GC thus losing the opportunity for surgery. For these patients, the efficacy of chemotherapy or radiotherapy even with targeted therapy are still limited (3). To break through the bottleneck of treatment, investigating the molecular mechanism of GC initiation and progression are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Deubiquitinating enzyme USP20 is a positive regulator of claspin and suppresses the malignant characteristics of gastric cancer cells

Wang

Yang

et al. 2017

International Journal of Oncology

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The aim of the present study was to investigate the clinical significance, the biological function and the mechanisms of USP20 in gastric cancer. The expression of USP20 in 89 pairs of primary gastric cancer and peritumoral gastric tissues specimens were measured by immunohistochemistry. The correlation of USP20 expression with the survival and the clinicopathological characteristics of patients were analyzed. Moreover, the underlying mechanisms of ectopic USP20 expression and its impact on GC cells were also investigated. We found that the expression of USP20 is relatively low in GC tissues and negatively correlated with tumor size, tumor invasion and TNM staging. High expression of USP20 in GC predicted longer survival. Experimentally, small interfering RNA-mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity. Overexpression of USP20 led to the inhibition of proliferation, G1-S cell cycle transition delay and autophagy activation. Mechanistically, we confirmed that silencing the expression of USP20 in GC cells could reduce Claspin protein levels without altering Claspin mRNA levels, which is involved in the antitumor activity of USP20. Furthermore, the expression level of Claspin was relatively higher in peritumoral tissue than that of GC tissues and higher expression of Claspin in GC was also correlated with good prognosis of patients. Given its pivotal role in gastric tumorigenesis and progression, USP20 functioned as the tumor suppressor in GC and possessed promising value to be a therapeutic target for GC.

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Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine

Cited by 9 publications

References 87 publications

Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric Cancer by Sponging miR-130a/miR-107 and Modulating PTEN

Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric Cancer by Sponging miR-130a/miR-107 and Modulating PTEN

Prognostic value of a novel FPR biomarker in patients with surgical stage II and III gastric cancer

Deubiquitinating enzyme USP20 is a positive regulator of claspin and suppresses the malignant characteristics of gastric cancer cells

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