BACKGROUND Gastric cancer(GC) is one of the main causes of cancer mortality worldwide.Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression.AIM To investi...BACKGROUND Gastric cancer(GC) is one of the main causes of cancer mortality worldwide.Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression.AIM To investigate whether lysyl oxidase(LOX) and hypoxia-inducible factor 1α(HIF1α) are prognostic and predictive biomarkers in GC.METHODS A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC.RESULTS Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases, deeper infiltration depth and later tumor–node–metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC.CONCLUSION LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.展开更多
目的:探讨赖氨酰氧化酶(lysyl oxidase,LOX)在卵巢癌中的表达模式、可能的作用机制,以及其表达与卵巢癌临床特征及治疗结局的相关性。方法:利用人类癌症基因组图谱(the Cancer Genome Atlas,TCGA)分析LOX表达与卵巢癌临床病理特征、治...目的:探讨赖氨酰氧化酶(lysyl oxidase,LOX)在卵巢癌中的表达模式、可能的作用机制,以及其表达与卵巢癌临床特征及治疗结局的相关性。方法:利用人类癌症基因组图谱(the Cancer Genome Atlas,TCGA)分析LOX表达与卵巢癌临床病理特征、治疗结局及预后的相关性;利用TISCH2数据库研究LOX在卵巢癌微环境不同细胞中的表达特征;免疫组化分析LOX在卵巢癌组织中的表达情况;利用siRNA转染技术沉默LOX基因,并通过转录组测序分析LOX沉默组及对照组细胞差异表达基因;通过基因集富集分析(gene set enrichment analysis,GSEA)LOX沉默组及对照组差异表达的信号通路蛋白并通过qRT-PCR验证;通过测定半数致死剂量(half-maximal inhibitory concentration,IC50)分析成纤维细胞中敲降LOX对卵巢癌紫杉醇敏感性的影响;通过Western blot及qRT-PCR分析紫杉醇作用下人纤维细胞和鼠纤维细胞中(L929)中LOX表达变化。结果:LOX高表达与卵巢癌的肿瘤存在、治疗结局差及静脉侵犯显著相关;在卵巢癌中,LOX在成纤维细胞中表达较高;沉默LOX可下调细胞黏附分子的表达;紫杉醇可诱导成纤维细胞中LOX表达上调;成纤维细胞中敲降LOX可增加共培养的成纤维细胞与肿瘤细胞对紫杉醇的敏感性。结论:LOX高表达与卵巢癌的不良预后相关,敲降LOX可提高卵巢癌对紫杉醇的化疗敏感性;其作用机制可能与改变成纤维细胞中细胞黏附分子表达相关;紫杉醇可上调成纤维细胞中LOX的表达。展开更多
基金Supported by the grants from the Military Medical Science and Technology Youth Training Program Project(16QNP146)
文摘BACKGROUND Gastric cancer(GC) is one of the main causes of cancer mortality worldwide.Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression.AIM To investigate whether lysyl oxidase(LOX) and hypoxia-inducible factor 1α(HIF1α) are prognostic and predictive biomarkers in GC.METHODS A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC.RESULTS Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases, deeper infiltration depth and later tumor–node–metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC.CONCLUSION LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.
