ns: not significant by Mann-Whitney test *: p < 0.05 by Mann-Whitney test ****: p < 0.0001 by Mann-Whitney test. ( d) Validation of Glut1 or Glut3 deletion by (upper panels) real-time PCR from purified CD45 - tumor fractions (KP & KPG1: n = 19, 32, respectively KP & KPG3: n = 14, 13, respectively KP & KPG1G3: n = 8, 10, respectively) or by (lower panels) Glut1 or Glut3 staining with IHC. ( c) Mouse models and viral vectors used. ( b) Representative Glut1 staining in a KP lung, showing weak expression in the alveolar compartment and strong staining in the bronchiolar epithelium. The number of lesions monitored per grade is indicated. (lower panel) IHC quantification of KP lesions from alveolar hyperplasia (AH) to grade 5 tumors shows percent of Glut1 staining defined as weak, intermediate or strong. ( a) (upper panels) Representative examples of Glut1 staining by immunohistochemistry (IHC) in KP tumors showing weak, intermediate or strong expression. ( h) Kaplan-Meier survival analysis of KP (n = 8) and KPG1 (n = 6) mice. Chi-square for trend was applied when comparing alveolar hyperplasia and adenomas, and adenocarcinomas. Fisher test was applied when comparing AH, grade 1, grade 2, grade 3, grade 4, and grade 5.
Adenocarcinomas contain the tumor grades 4 and 5. Alveolar hyperplasia and adenomas include the AH and the tumor grades 1, 2, and 3.
( g) Percent of KP (n = 128) and KPG1 (n = 102) lesions classified by tumor grades, either detailed from alveolar hyperplasia (AH) to grade 5 or discriminated between alveolar hyperplasia and adenomas, and adenocarcinomas. ns: not significant by Mann-Whitney test. shows the average number of KP and KPG1 tumors per mouse (n = 7 and 6 mice). shows KP and KPG1 tumor weights (n = 17 and 21) at sacrifice 29 weeks post-tumor initiation. shows the fold changes of KP and KPG1 tumor volumes (n = 32 and 26, respectively) monitored during 28 days by μCT, starting at 16 weeks and 6 days post-tumor initiation with tumor volumes set to 1. Percent of TP53 mutation in each subtype is indicated. ( c) Expression level (log2 normalized) of SLC2A1 and SLC2A3 in the 4 NMF LUAD subtypes. The number of cases per score and histology are indicated. ( b) Immunohistochemistry (IHC) from a next-generation tissue microarray of human LUAD and LUSC showing score 1 (intermediate) or score 2 (strong) GLUT1 staining. ( a) Gene expression level (RSEM) of glucose transporters in TCGA-LUAD samples (n = 511).