Transcriptome foundations of high FDG uptake in lung cancer

Objectives The molecular basis of increased lung cancer glycolysis has not been comprehensively assessed. We examined the RNA transcriptomes of lung cancer vs. normal lung using microarray approaches with special emphasis on major cellular functional pathways.

Methods 58 cancer and 49 normal lung tissues transcriptomes from lung cancer study (GSE10072) was selected from the public GEO dataset. Affymetrix U133-A chips were used (14,500 well characterized genes). After RMA normalization, Spotfire software analysis was performed. Each volume change of major metabolic pathways was estimated with X² test using Stata software.

Results Comparing gene profiles of cancer with normal tissues, 44 out of 77 probesets in glycolysis were up, and 4 probe sets down in the cancer group. The balance of the change shifted to increase the volume in glycolysis and gluconeogenesis pathways. In Krebs-TCA , 20 out of 54 probesets up and 2 down in lung cancer were recorded which led to the same directional move as in the glycolysis pathway. One metric of glycolysis and TCA increased activity was VDAC overexpression which is associated with de novo nucleotide synthesis. Both the pentose phosphate pathway and nucleotide metabolism messages increased significantly in cancer vs normal lung. In the cell cycle pathway, 85/154 probesets in lung cancer were increased and 14/154 probesets were decreased. The other line of evidence of proliferation increase in lung cancer was Ki67 and PCNA which were over expression.

Conclusions In addition to glycolysis; gluconeogenesis, pentose phosphate shunt, Krebs cycle and proliferation transcriptomes are upregulated in lung cancer.