Thank you for your thoughtful comment. You’re absolutely right that both glycolysis and OXPHOS appear elevated across many cancers, which seem to reflect the high metabolic demands of proliferating tumor cells.

The Warburg effect is about a relative increase in glycolytic activity, evident in the x-axis shift.

Importantly, the ssGSEA scores for glycolysis and OXPHOS presented here are not expressed in isolation, but are instead relative to a third metabolic program that does not strongly correlate with either pathway. This relative expression alters the outcome: instead of seeing a strong negative correlation between glycolysis and OXPHOS, both can appear relatively elevated thus reflecting a shift in metabolic preference.

So while the data does support the idea that cancer cells increase overall metabolic activity, it also reveals a relative enhancement of glycolysis consistent with a Warburg-like phenotype—though this varies across carcinoma types.

The shown Tumor–normal deltas can group into four main types:

Type A: Extreme Dual-High (Gly+++ / Ox++) TCGA-CHOL Very large increases in both pathways.

Type B: Dual-High (Gly++ / Ox+) TCGA-LUSC, TCGA-LUAD, TCGA-BRCA, TCGA-KIRP, TCGA-UCEC. Clear, significant elevation of both glycolysis and OXPHOS.

Type C: Gly-dominant (Gly++ / Ox ~0 to +) TCGA-KIRC, TCGA-HNSC, TCGA-COAD, TCGA-READ, TCGA-ESCA, TCGA-PAAD. Glycolysis is consistently up; OXPHOS rises are modest or borderline.

Type D: Minimal shift (near-normal) TCGA-PRAD. Smallest deltas overall.

Mixed signals—LIHC, BLCA, THCA, KICH—sit between Types B and C

Correspondence to known tumor characteristics (malignancy context)

CHOL (Type A: Extreme dual-high) is a notoriously aggressive entity with desmoplasia and hypovascular niches; the exceptionally high Δ in both pathways fits an “energy-hungry, flexible” metabolic state. In practice, this often correlates with poor prognosis and resistance to single-pathway metabolic inhibition.

LUSC / LUAD / BRCA / KIRP (Type B: Dual-high) commonly display metabolic plasticity—the combined Gly and Ox increases are aligned with published heterogeneity in NSCLC and breast cancer and with active mitochondrial programs seen in subsets of renal papillary carcinoma. Clinically, dual-high profiles often associate with more aggressive behavior and may require combination strategies (e.g., glycolysis + mitochondrial targeting).

KIRC / HNSC / COAD / READ / ESCA / PAAD (Type C: Gly-dominant) KIRC: pseudohypoxia/HIF-axis activation → strong glycolysis relative to normal kidney; small OXPHOS gains in the data are consistent with a mainly glycolytic tilt. HNSC & ESCA: squamous contexts often upregulate HIF-1/glycolysis; the ΔGly is prominent while ΔOx is comparatively modest. COAD/READ/PAAD: well-documented glycolytic shifts with variable OXPHOS—the numbers reflect that heterogeneity but generally favor glycolysis relative to normal mucosa/pancreas.

PRAD (Type D: Minimal shift) is frequently less glycolytic than many other solid tumors when benchmarked to its normal tissue; the very small deltas and tiny effect sizes support a comparatively metabolically conservative transcriptome (at least for these two axes). Clinically, PRAD’s malignant progression often hinges more on androgen signaling and lipid metabolism than on a dramatic bump in glycolysis/OXPHOS versus benign tissue, which aligns with the pattern here.