Impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification

Abstract

Abstract. High expression levels of glucose transporter isoform 1 (GLUT1) and Ki-67 are reportedly associated with malignancy-related clinicopathological factors in malignant tumors. Recently, a new histological IASLC/ATS/ERS classification for lung adenocarcinoma was proposed. In this study, we investigated the clinicopathological impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma classified according to the IASLC/ATS/ERS classification. One hundred and five patients with completely resected stage IA lung adenocarcinoma were retrospectively classified into two groups, a ʻnon-invasive typeʼ (n=31) or an ʻinvasive typeʼ (n=74), based on the IASLC/ATS/ERS classification. GLUT1 and Ki-67 expression status was evaluated using immunohistochemistry. The epidermal growth factor receptor (EGFR) and KRAS mutation status was determined using PCR-based assays. Positive GLUT1 and Ki-67 expression and EGFR and KRAS mutations were detected in 28 (27%), 33 (31%), 51 (49%) and 5 (8%) cases, respectively. Positive GLUT1 expression was significantly associated with a wildtype EGFR and mutant KRAS status. A multivariate analysis revealed that positive GLUT1 expression was independently associated with the ʻinvasive typeʼ. In multivariate analyses for overall survival (OS) and disease-free survival (DFS), positive Ki-67 and GLUT1 expression was the only independent factor for a poor OS (P=0.012) and DFS (P=0.040), respectively. In addition, when stratified according to the GLUT1 and Ki-67 status, double-positive cases had the poorest DFS and OS times, compared with the other categories. Positive GLUT1 expression is associated with the invasive character of earlystage lung adenocarcinoma and with early disease relapse. Our results strongly suggest that GLUT1 and Ki-67 play important roles in acquiring biological malignant potential in early-stage lung adenocarcinoma.

Hyperglycemia Promotes K-Ras-Induced Lung Tumorigenesis through BASCs Amplification

“…However, our studies provide new insight into a largely unappreciated role for hyperglycemia in the regulation of tumor-initiating BASCs behavior. In this regard, it is interesting to note that Glut1 expression has been observed to be elevated in oncogenic K-Ras-positive human lung adenocarcinomas [31], suggesting that our results may also be translated in human malignancy.The tumor-promoting activity of hyperglycemia on tumor-initiating BASCs can be mediated by direct and indirect mechanisms. Hyperglycemia induces oxidative stress and ROS (reactive oxygen species) production [29].…”

Prognostic impact of the combination of glucose transporter 1 and ATP citrate lyase in node-negative patients with non-small lung cancer

“…In particular, GLUT1 overexpression has been reported in NSCLC, and correlations between GLUT1 expression and a number of clinical parameters such as gender, smoking status, tumor size, pathological subtypes, differentiation and poor prognosis have been demonstrated in NSCLC patients [13][14][15][16][17]. It has also been reported that the overexpression of ACLY correlates with advanced stage, the presence of pleural invasion, poor differentiation, and poor outcome in patients with lung adenocarcinoma [18].…”

“…Upregulation of both GLUT1 and ACLY has been shown in various types of tumors, including breast, colorectal, gastric cancer and hepatocellular carcinoma [9][10][11][12]. Notably, overexpression of both GLUT1 and ACLY is significantly associated with poor survival in patients with NSCLC [13][14][15][16][17][18].…”

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

“…11 studies compared the DFS between EGFR mutations and wild-type groups [18], [22], [12], [25], [26], [27], [28], [29], [30], [31], [33]. Significant heterogeneity was detected among the studies (I 2  = 62%, P  = 0.003).…”

“…Fixed-effect model was used in subgroup analysis. Multivariate analysis was used by 6 studies [18], [22], [12], [25], [26], [33], and univariate analysis was used in 4 studies [28], [29], [30], [31]. There was no significant association between EGFR mutations and DFS (multivariate analysis HR = 0.89, 95% CI [0.71–1.12] P  = 0.32; univariate analysis HR = 1.15, 95% CI [0.79–1.67] P  = 0.46 Figure 3).…”