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GLUT1 的过表达与肺腺癌中的 Kras 突变相关。

Overexpression of GLUT1 correlates with Kras mutations in lung carcinomas.

机构信息

Department of Oncology, Immunology and Surgery, Nagoya City University, Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

出版信息

Mol Med Rep. 2012 Mar;5(3):599-602. doi: 10.3892/mmr.2011.736. Epub 2011 Dec 22.

Abstract

Glucose is the major source of energy for cells, and glucose transporter 1 (GLUT1) is the most common glucose transporter. GLUT1 has been found to be aberrantly expressed in several tumor types. From the results of the microarray and serial analysis of gene expression (SAGE), GLUT1 transcript expression was found to be higher in clones with mutant Kras alleles. We hypothesized that GLUT1 overexpression might be correlated with clinicopathological features of Japanese lung cancers. Immunohistochemistry for GLUT1 was performed in 283 surgically treated non-small cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Thirty-six Kras mutant carcinoma cases were included. GLUT1 overexpression was found in 138 (48.8%) lung cancer patients. The GLUT1 overexpression status was significantly correlated with gender (women 31.9% vs. men 54.5%, P<0.0001), smoking status (never smoker 31.4% vs. smoker 59.4%, P<0.0001) and pathological subtypes (adenocarcinoma 36.4% vs. non‑adenocarcinoma 74.5%, P<0.0001). In addition, the GLUT1 overexpression status was significantly correlated with gene mutation status, including EGFR (mutation-positive 23.4% vs. -negative 58.3%, P<0.0001) and Kras (mutation-positive 66.7% vs. -negative 46.6%, P=0.038). The survival of patients with GLUT1 overexpression (n=137, 50 were deceased) was significantly worse when compared to the patients with normal expression of GLUT1 (n=142, 31 were deceased) (Log-rank test, P=0.0009). Thus, GLUT-1 overexpression correlates with an aggressive phenotype of lung carcinoma.

摘要

葡萄糖是细胞的主要能量来源,葡萄糖转运蛋白 1(GLUT1)是最常见的葡萄糖转运蛋白。已经发现 GLUT1 在几种肿瘤类型中异常表达。通过微阵列和基因表达序列分析(SAGE)的结果,发现具有突变 Kras 等位基因的克隆中 GLUT1 转录表达更高。我们假设 GLUT1 过表达可能与日本肺癌的临床病理特征相关。在名古屋城市大学医院的 283 例接受手术治疗的非小细胞肺癌(NSCLC)病例中进行了 GLUT1 的免疫组织化学检查。包括 36 例 Kras 突变癌病例。在 138 例(48.8%)肺癌患者中发现 GLUT1 过表达。GLUT1 过表达状态与性别(女性 31.9%比男性 54.5%,P<0.0001)、吸烟状况(从不吸烟者 31.4%比吸烟者 59.4%,P<0.0001)和病理亚型(腺癌 36.4%比非腺癌 74.5%,P<0.0001)显著相关。此外,GLUT1 过表达状态与基因突变状态显著相关,包括 EGFR(突变阳性 23.4%比阴性 58.3%,P<0.0001)和 Kras(突变阳性 66.7%比阴性 46.6%,P=0.038)。与 GLUT1 正常表达的患者(n=142,31 例死亡)相比,GLUT1 过表达(n=137,50 例死亡)的患者的生存时间显著更差(Log-rank 检验,P=0.0009)。因此,GLUT-1 过表达与肺癌侵袭性表型相关。

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