Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Department of Food Science & Nutrition, Graduate School of Home Economics, Kyoritsu Women's University, Tokyo, Japan.
Thorac Cancer. 2023 Sep;14(27):2761-2769. doi: 10.1111/1759-7714.15060. Epub 2023 Aug 7.
Glucose transporters (GLUTs) are highly expressed in various cancers. However, the implications of these variable expression patterns are unclear. This study aimed to clarify the correlation between class I GLUT expression patterns and clinical outcomes in non-small cell lung cancer (NSCLC), including their potential role in inflammatory signaling.
Biopsy tissues from 132 patients with NSCLC (92 adenocarcinomas [ADC] and 40 squamous cell carcinomas [SQCC]) were analyzed. mRNA expression levels of class I GLUTs (solute carrier 2A [SLC2A]1, SLC2A2, SLC2A3, and SLC2A4) and inflammation-related molecules (toll-like receptors TLR4, RelA/p65, and interleukins IL8 and IL6) were measured. Cellular localization of GLUT3 and GLUT4 was investigated using immunofluorescence.
Single, combined, and negative GLUT (SLC2A) expression were observed in 27/92 (29.3%), 27/92 (29.3%), and 38/92 (41.3%, p < 0.001) of ADC and 8/40 (20.0%), 29/40 (72.5%, p < 0.001), and 3/40 (7.5%) of SQCC, respectively. In ADC, the single SLC2A3-expressed group had a significantly poorer prognosis, whereas the single SLC2A4-expressed group had a significantly better prognosis. The combined expression groups showed no significant difference. SLC2A expression was not correlated with SQCC prognosis. SLC2A4 expression correlated with lower IL8 expression. GLUT3 and GLUT4 expressions were localized in the tumor cytoplasm.
In lung ADC, single SLC2A3 expression correlated with poor prognosis, whereas single SLC2A4 expression correlated with better prognosis and lower IL8 expression. GLUT3 expression, which is increased by IL8 overexpression, may be suppressed by increasing the expression of GLUT4 through decreased IL8 expression.
葡萄糖转运蛋白（GLUTs）在各种癌症中高度表达。然而，这些可变表达模式的意义尚不清楚。本研究旨在阐明 I 类 GLUT 表达模式与非小细胞肺癌（NSCLC）临床结局之间的相关性，包括它们在炎症信号中的潜在作用。
分析了 132 例 NSCLC（92 例腺癌[ADC]和 40 例鳞状细胞癌[SQCC]）患者的活检组织。测量了 I 类 GLUT（溶质载体 2A [SLC2A]1、SLC2A2、SLC2A3 和 SLC2A4）和炎症相关分子（Toll 样受体 4、RelA/p65 和白细胞介素 8 和白细胞介素 6）的 mRNA 表达水平。使用免疫荧光法研究 GLUT3 和 GLUT4 的细胞定位。
在 ADC 中，单、组合和阴性 GLUT（SLC2A）表达分别观察到 27/92（29.3%）、27/92（29.3%）和 38/92（41.3%）（p<0.001），而在 SQCC 中分别为 8/40（20.0%）、29/40（72.5%）和 3/40（7.5%）（p<0.001）。在 ADC 中，单 SLC2A3 表达组的预后明显较差，而单 SLC2A4 表达组的预后明显较好。组合表达组之间无显著差异。SLC2A 表达与 SQCC 预后无关。SLC2A4 表达与较低的 IL8 表达相关。GLUT3 和 GLUT4 的表达定位于肿瘤细胞质中。
在肺 ADC 中，单 SLC2A3 表达与预后不良相关，而单 SLC2A4 表达与预后较好和较低的 IL8 表达相关。IL8 过表达增加 GLUT3 表达，可能通过降低 IL8 表达增加 GLUT4 表达而受到抑制。
