Fig. 5
Association of the lipid metabolism enzyme ELOVL2 to patient clinical outcome and GBM development. a High ELOVL2 expression is associated with worse patient survival. GBM tissue transcriptomes (microarrays) of 485, 156 and 173 GBMs of TCGA, French and Rembrandt datasets, respectively. Log-rank (Mantel-Cox) test. b Decreased ELOVL2 mRNA levels in shELOVL2 patient-derived cells (PDC) compared to shControl-PDC. 6240**, R633 and 5706** PDC. QPCR assay. Unpaired t-test with Welch’s correction, mean ± SD, n = 4–5 independent biological samples. c ELOVL2 knockdown decreases cell proliferation. 6240**, R633 and 5706** PDC. Unpaired t-test with Welch’s correction, mean ± SD, n = 4–5 independent biological samples. d ELOVL2 knockdown delays tumor development. Bioluminescent analyses of tumor growth initiated by grafting PDC transduced with a luciferase construct and either shControl (shCTL) or shELOVL2 constructs. n = 4 (6240**) and n = 6–8 (5706**) mice per group. e ELOVL2 knockdown decreases tumor burden as shown by quantification of the tumor bioluminescent signals. DPG: days post-graft. n = 4 (6240**) and n = 6–8 (5706**) mice per group. Mean ± SD. Unpaired t-test with Welch’s correction. Background signal (mean ± SD): 6240** 537 ± 68, n = 8, 5706** 589 ± 59, n = 14 mice. f Recovery of ELOVL2 expression in tumors forming from xenografts of 6240** shELOVL2. QPCR assay. Mean ± SD. n = 4 for shCTL and n = 3 for shELOVL2. Unpaired t-test with Welch’s correction. g-k Principal curve resulting from PCA of the expression of the subgroup of genes encoding lipid metabolism enzymes overexpressed in TumHIGH cells and tissues. g Cell density along the principal curve. The ellipse delineates the portion of the curve with the highest cell density. h-k Cells colored according to their (h) score calculated with the components of the lipid subgroup, (i) ELOVL2 expression levels, (j) tumorigenic score, and (k) extracellular vesicle biogenesis score. Note that cells with either high score or expression value cluster on the same portion of the curve (ellipses). Pathifier tool