Figure 1: TCA cycle metabolism is upregulated in HGSC, and increased expression of IDH1 correlates with decreased progression-free survival of HGSC patients.

(A) LC/MS comparison of 2 FT (FT282 and FT4-Tag) and 2 HGSC (Ovcar3 and Ovcar10) cell lines. Heat map shows z-scores of relative abundance normalized to the mean of each individual TCA cycle metabolite. Significant metabolites are labeled in green. Adjusted p-value (FDR) <0.05.

(B) Differentially expressed transcripts in 5 FT (FT282, FT4-Tag, FT6-Tag, FT33-Tag, and PFTE4) and 2 HGSC (Ovcar3 and Ovcar10) cell lines. Heat map shows z-scores of expression levels relative to B2M of 27 TCA cycle enzymes. Significant transcripts are labeled in green. Adjusted p-value (FDR) <0.05

(C) Differentially expressed transcripts of 27 TCA cycle enzymes. Heat map shows fold change of averaged z-scores of Ovcar3 and Ovcar10 cultured in adherent versus ultra-low attachment conditions. The qPCR for adherent vs. spheroid was performed at the same time with the same conditions. Significantly upregulated transcripts are labeled in green. Adjusted p-value (FDR) <0.001.

(D) Kaplan-Meier curve for progression-free survival of ovarian cancer patients classified according to IDH1 expression level. Ovarian cancer patients were filtered for a serous histosubtype and TP53 mutation. Hazard ratio (HR) and logrank p-values are indicated.

(E) Immunoblot analysis of IDH1 comparing normal human FT and HGSC patient tissue lysates. Vinculin was used as a loading control.

(F) IDH1 protein expression normalized to vinculin and quantified using ImageJ. Data represent mean ± SD. *p<0.03.

(G) IDH1 mRNA expression from a publicly-available dataset comparing fallopian tube and matched HGSC patient samples (GSE10971). *p<0.0006.