基于公共数据库分析脯氨酸羟化酶3在非小细胞肺癌中的表达及预后价值
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摘要
目的:探讨脯氨酸羟化酶3(prolyl hydroxylase 3,PHD3)在非小细胞肺癌中的表达及预后价值。方法:应用Oncomine和Gene Expression Omnibus (GEO)数据库对PHD3 mRNA在NSCLC中表达水平及其与临床病理参数的关系进行分析,通过Kaplan-Meier Plotter和SurvExpress分析PHD3 mRNA表达水平与NSCLC预后的关系。结果:PHD3 mRNA在NSCLC组织中高表达(P=0.028)。PHD3高表达与鳞癌亚型,较晚的临床分期和男性患者相关(P<0.001,P=0.001)。Kaplan-Meier Plotter分析显示PHD3高表达提示腺癌较差的总生存率(P=0.003),SurvExpress分析结果也显示PHD3主要影响腺癌的预后(P=0.013),且在高危组中其表达水平显著上调(P<0.001)。Kaplan-Meier Plotter和SurvExpress分析结果均显示PHD3 mRNA表达水平与鳞癌预后无相关性。结论:PHD3可以作为一个潜在的分子标记预测NSCLC主要是肺腺癌的预后。
Objective: To investigates the expression and prognostic value of prolyl hydroxylase 3(PHD3) in non-small cell lung cancer(NSCLC). Methods: Oncomine and Gene Expression Omnibus(GEO) databases were used to determine the expression level of PHD3 mRNA in NSCLC. The expression level and prognostic value of PHD3 mRNA was determined by Kaplan-Meier Plotter and SurvExpress database. Results: The expression levels of PHD3 mRNA were significantly up-regulated in NSCLC compared with normal tissue(P=0.028). High expression level of PHD3 was associated with lung squamous cell carcinoma(LUSC), advanced stages and male patients(P<0.001,P=0.001;respectively).The results of Kaplan-Meier Plotter revealed that the high PHD3 expression group exhibited poorer survival in lung adenocarcinoma(LUAD) patients(P=0.003).The SurvExpress analysis also showed that PHD3 mainly affected the prognosis of LUAD patients(P=0.013), and that PHD3 expression was significantly elevated in the high-risk group(P<0.001). Kaplan-Meier plotter and SurvExpress analyses suggested that PHD3 mRNA expression was not associated with survival in LUSC patients. Conclusion: PHD3 might serve as a potential biomarker to predict survival of NSCLC, mainly of LUAD.
Objective: To investigates the expression and prognostic value of prolyl hydroxylase 3(PHD3) in non-small cell lung cancer(NSCLC). Methods: Oncomine and Gene Expression Omnibus(GEO) databases were used to determine the expression level of PHD3 mRNA in NSCLC. The expression level and prognostic value of PHD3 mRNA was determined by Kaplan-Meier Plotter and SurvExpress database. Results: The expression levels of PHD3 mRNA were significantly up-regulated in NSCLC compared with normal tissue(P=0.028). High expression level of PHD3 was associated with lung squamous cell carcinoma(LUSC), advanced stages and male patients(P<0.001,P=0.001;respectively).The results of Kaplan-Meier Plotter revealed that the high PHD3 expression group exhibited poorer survival in lung adenocarcinoma(LUAD) patients(P=0.003).The SurvExpress analysis also showed that PHD3 mainly affected the prognosis of LUAD patients(P=0.013), and that PHD3 expression was significantly elevated in the high-risk group(P<0.001). Kaplan-Meier plotter and SurvExpress analyses suggested that PHD3 mRNA expression was not associated with survival in LUSC patients. Conclusion: PHD3 might serve as a potential biomarker to predict survival of NSCLC, mainly of LUAD.
引文
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[16] Ognibene M,Cangelosi D,Morini M,et al.Immunohistochemical analysis of PDK1,PHD3 and HIF-1alpha expression defines the hypoxic status of neuroblastoma tumors[J].PLoS One,2017,12(11)∶e0187206.
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[18] Chen S,Zhang J,Li X,et al.The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer[J].Mol Cell Biochem,2011,358(1-2)∶257-263.
[19] Giatromanolaki A,Koukourakis MI,Pezzella F,et al.Expression of prolyl-hydroxylases PHD-1,2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activated HIF pathway[J].Cancer Lett,2008,262(1)∶87-93.
[20] Wong CC,Qian Y,Yu J.Interplay between epigenetics and metabolism in oncogenesis:mechanisms and therapeutic approaches[J].Oncogene,2017,36(24)∶3359-3374.
[21] Shoshan-Barmatz V,Bishitz Y,Paul A,et al.A molecular signature of lung cancer:potential biomarkers for adenocarcinoma and squamous cell carcinoma[J].Oncotarget,2017,8(62)∶105492-105509.
[22] Chang JT,Lee YM,Huang RS.The impact of the Cancer Genome Atlas on lung cancer[J].Transl Res,2015,166(6)∶568-585.
[2] Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J].CA Cancer Clin,2015,65(1)∶5-29.
[3] Ettinger DS,Wood DE,Aisner DL,et al.Non-Small Cell Lung Cancer,Version 5.2017,NCCN Clinical Practice Guidelines in Oncology[J].J Natl Compr Canc Netw,2017,15(4)∶504-535.
[4] Jiang L,Liu QL,Liang QL,et al.Association of PHD3 and HIF2alpha gene expression with clinicopathological characteristics in human hepatocellular carcinoma[J].Oncol Lett,2018,15(1)∶545-551.
[5] Singh D,Arora R,Kaur P,et al.Overexpression of hypoxia-inducible factor and metabolic pathways:possible targets of cancer[J].Cell Biosci,2017,7:62.
[6] Urrutia AA,Aragones J.HIF oxygen sensing pathways in lung biology[J].Biomedicines,2018,6(2)∶68.
[7] Miikkulainen P,Hogel H,Rantanen K,et al.HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma[J].Cancer Metab,2017,5∶5.
[8] Peurala E,Koivunen P,Bloigu R,et al.Expressions of individual PHDs associate with good prognostic factors and increased proliferation in breast cancer patients[J].Breast Cancer Res Treat,2012,133(1)∶179-188.
[9] Xia YJ,Jiang XT,Jiang SB,et al.PHD3 affects gastric cancer progression by negatively regulating HIF1A[J].Mol Med Rep,2017,16(5)∶6882-6889.
[10] Su Y,Loos M,Giese N,et al.PHD3 regulates differentiation,tumour growth and angiogenesis in pancreatic cancer[J].Br J Cancer,2010,103(10)∶1571-1579.
[11] Andersen S,Donnem T,Stenvold H,et al.Overexpression of the HIF hydroxylases PHD1,PHD2,PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival[J].PLoS One,2011,6(8)∶e23847.
[12] Dopeso H,Jiao HK,Cuesta AM,et al.PHD3 controls lung cancer metastasis and resistance to EGFR inhibitors through TGFalpha[J].Cancer Res,2018,78(7)∶1805-1819.
[13] Rhodes DR,Yu J,Shanker K,et al.ONCOMINE:a cancer microarray database and integrated data-mining platform[J].Neoplasia,2004,6(1)∶1-6.
[14] Gyorffy B,Surowiak P,Budczies J ,et al.Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer[J].PLoS One,2013,8(12)∶e82241.
[15] Aguirre-Gamboa R,Gomez-Rueda H,Martinez-Ledesma E,et al.SurvExpress:an online biomarker validation tool and database for cancer gene expression data using survival analysis[J].PLoS One,2013,8(9)∶e74250.
[16] Ognibene M,Cangelosi D,Morini M,et al.Immunohistochemical analysis of PDK1,PHD3 and HIF-1alpha expression defines the hypoxic status of neuroblastoma tumors[J].PLoS One,2017,12(11)∶e0187206.
[17] Lin YH,Chang KP,Lin YS,et al.Pretreatment combination of platelet counts and neutrophil-lymphocyte ratio predicts survival of nasopharyngeal cancer patients receiving intensity-modulated radiotherapy[J].Onco Targets Ther,2017,10∶2751-2760.
[18] Chen S,Zhang J,Li X,et al.The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer[J].Mol Cell Biochem,2011,358(1-2)∶257-263.
[19] Giatromanolaki A,Koukourakis MI,Pezzella F,et al.Expression of prolyl-hydroxylases PHD-1,2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activated HIF pathway[J].Cancer Lett,2008,262(1)∶87-93.
[20] Wong CC,Qian Y,Yu J.Interplay between epigenetics and metabolism in oncogenesis:mechanisms and therapeutic approaches[J].Oncogene,2017,36(24)∶3359-3374.
[21] Shoshan-Barmatz V,Bishitz Y,Paul A,et al.A molecular signature of lung cancer:potential biomarkers for adenocarcinoma and squamous cell carcinoma[J].Oncotarget,2017,8(62)∶105492-105509.
[22] Chang JT,Lee YM,Huang RS.The impact of the Cancer Genome Atlas on lung cancer[J].Transl Res,2015,166(6)∶568-585.