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喉癌中的氟脱氧葡萄糖摄取与葡萄糖转运蛋白-1、缺氧诱导因子-1α的表达以及磷酸肌醇3激酶/蛋白激酶B信号通路有关。

Fluorodeoxyglucose uptake in laryngeal carcinoma is associated with the expression of glucose transporter-1 and hypoxia-inducible-factor-1α and the phosphoinositide 3-kinase/protein kinase B pathway.

作者信息

Zhao Kui, Yang Shu-Ye, Zhou Shui-Hong, Dong Meng Jie, Bao Yang-Yang, Yao Hong-Tian

机构信息

Department of PET Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

出版信息

Oncol Lett. 2014 Apr;7(4):984-990. doi: 10.3892/ol.2014.1877. Epub 2014 Feb 12.

Abstract

High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is believed to be an intrinsic marker of hypoxia in malignant tumors. The expression of hypoxia-inducible factor-1α (HIF-1α) and correlated target genes, including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling pathway is involved in regulating FDG uptake directly. In the present study, 24 consecutive patients with laryngeal carcinoma were examined pre-operatively and the standardized uptake values (SUV) of the laryngeal carcinomas were determined. Glut-1, HIF-1α, PI3K and phosphorylated-Akt (p-Akt) expression was detected by immunohistochemical staining of paraffin sections from the tumor specimens. Associations among SUV, Glut-1, HIF-1α, PI3K and p-Akt protein expression and the other clinical parameters were analyzed. The univariate analyses revealed a significantly shorter survival time along with higher HIF-1α (P=0.018) and PI3K (P=0.008) expression, but the survival time was not significantly correlated with Glut-1 or p-Akt expression. The multivariate analysis demonstrated that higher SUV (P=0.043) and PI3K expression (P=0.012) were significantly correlated with a poor survival time. Spearman's rank analysis showed significant correlations between SUV and HIF-1α (r=0.577; P=0.003), PI3K (r=1.0; P<0.0001) and p-Akt (r=0.577; P=0.003) expression. PI3K was associated with poorly- and moderately-differentiated laryngeal carcinoma (P=0.012). In conclusion, a high SUV indicates a poor prognosis for laryngeal carcinoma. Also, a high SUV may be associated with the increased expression of Glut-1, HIF-1α, PI3K and p-Akt.

摘要

包括头颈癌在内的人类癌症中,高氟脱氧葡萄糖(FDG)摄取与预后不良相关。葡萄糖转运蛋白1(Glut-1)被认为是恶性肿瘤缺氧的内在标志物。缺氧诱导因子-1α(HIF-1α)及相关靶基因(包括Glut-1)的表达受磷酸肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路调控。然而,PI3K/Akt信号通路是否直接参与调节FDG摄取仍不清楚。在本研究中,对24例连续的喉癌患者进行术前检查,并测定喉癌的标准化摄取值(SUV)。通过对肿瘤标本石蜡切片进行免疫组化染色,检测Glut-1、HIF-1α、PI3K和磷酸化Akt(p-Akt)的表达。分析SUV、Glut-1、HIF-1α、PI3K和p-Akt蛋白表达与其他临床参数之间的相关性。单因素分析显示,HIF-1α(P=0.018)和PI3K(P=0.008)表达较高时,生存时间显著缩短,但生存时间与Glut-1或p-Akt表达无显著相关性。多因素分析表明,较高的SUV(P=0.043)和PI3K表达(P=0.012)与较差的生存时间显著相关。Spearman等级分析显示,SUV与HIF-1α(r=0.577;P=0.003)、PI3K(r=1.0;P<0.0001)和p-Akt(r=0.577;P=0.003)表达之间存在显著相关性。PI3K与低分化和中分化喉癌相关(P=0.012)。总之,高SUV提示喉癌预后不良。此外,高SUV可能与Glut-1、HIF-1α、PI3K和p-Akt表达增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f6/3961369/69f81a02d6f6/OL-07-04-0984-g00.jpg

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