Skip to main content
. Author manuscript; available in PMC: 2022 Oct 18.
Published in final edited form as: Nat Cancer. 2022 Apr 18;3(6):681–695. doi: 10.1038/s43018-022-00360-7

Figure 3 -. XPR1 and SLC34A2 expression in patient samples indicate cancer-specific phosphate dysregulation caused by the lineage survival transcription factor PAX8.

Figure 3 -

a) SLC34A2 is expressed in ovarian and uterine tumor samples at sufficient levels to predict dependency on XPR1. RNA expression values for SLC34A2 were compared within the idicated lineages. XPR1 dependency status is indicated by color where applicable (CERES < −0.5). q-values indicate the likelihood of the indicated populations having the same SLC34A2 expression according to a two-sided Wilcoxon ranked sums test with Bonferroni correction for multiple comparisons. Boxplots are drawn indicating the first and third quartiles, and whiskers span to the largest value within 1.5x the interquartile range. See methods for exact N values.

b) The expression of SLC34A2 was measured using RNAseq (N=1) after stable overexpression of PAX8 as indicated (PAX8 O/E), and induction of a PAX8-targeting (sg4) or control (sg9) sgRNA and dCas9-KRAB.

c) Seven days after transduction with the indicated sgRNA (N=2, separate transductions), RNA was extracted, converted to cDNA, and the expression of SLC34A2 was measured using RT-PCR. Significance was assessed by comparing the expression relative to sgChr2-2 across two cell lines with a one-tailed t-test, and corrected for multiple comparisons using the Bonferroni method. Data are representative of N=2 independent experiments.

d) XPR1 copy number heatmap for a ~2.5 Mb region of chromosome 1 indicating XPR1 amplification in TCGA serous ovarian cancer22. Each patient sample is represented by a horizontal line. Red indicates copy gain and blue indicates copy loss. Dashed vertical lines are the location of indicated genes. Data are a subset of the 489 samples, rank ordered by highest copy gain to indicate both focal and chromosome arm variants.

e) XPR1 mRNA expression is increased in ovarian and uterine cancer. XPR1 mRNA expression values from the same sources as panel a are compared for the indicated tissues, with TCGA OV and TCGA UCEC color-coded by XPR1 copy number status as determined by GISTIC analysis. Boxplots are drawn as in a. Statistical differences between tissues were determined as in a. The correlation of XPR1 copy number and expression was performed using spearman’s ranked correlation test. See methods for exact N values.