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. 2019 May 3;8:e44306. doi: 10.7554/eLife.44306

Figure 1. COPA identifies a lineage-specific PAX8 regulon in ovarian cancer.

(A) TumorMap analysis visualizing RNAseq-based transcriptional compendium of human cancer cell lines. Each dot in the map represented a cancer cell line. Colors indicated different tissues of origin. (B) The indicated putative lineage-survival oncogenes were overlaid to cancer cell lines in which they were identified as outlier genes. Note that they displayed enrichment in the previously reported tumor types. (C) Immunohistochemical staining of PAX8 in tissue microarrays containing 674 ovarian cancer cases. Left panel showed representative IHC images. Quantification in the right panel indicated that PAX8 was expressed in various histotypes of ovarian carcinomas, but not adjacent or normal tissues. (D) Confined gene expression of the PAX8 regulon in ovarian cancer cell lines. (E) Confined gene expression of the PAX8 regulon in TCGA ovarian tumor tissues. (F) Regulatory network of the PAX8 regulon as inferred by individually knocking out each member with CRISPR-Cas9 system and quantifying relative gene expression in ovarian cancer cells.

Figure 1.

Figure 1—figure supplement 1. COPA identified PAX8 as an outlier gene in ovarian cancer.

Figure 1—figure supplement 1.

(A) Thresholds (black lines) used for cancer outlier profile analysis. X and Y axes indicated the range and density of outlier scores, respectively. (B) Plot of nominated outlier genes across all cancer cell lines (sample-wise comparison) and among genome-wide mRNA measurements in a given sample (gene-wise comparison). Each color represented a different tissue of origin. (C) Focal amplification of PAX8 gene in a subset of TCGA ovarian carcinomas. (D) Hematoxylin and eosin (H and E) staining of tissue microarrays containing 674 epithelial ovarian cancer samples.
Figure 1—figure supplement 2. PAX8 regulon gene expression in cell lines and TCGA tumor tissues.

Figure 1—figure supplement 2.

(A) Boxplots of PAX8 regulon gene expression in cancer cell lines. (B) Boxplots of PAX8 regulon gene expression in TCGA tumor tissues.
Figure 1—figure supplement 3. PAX8 regulon gene expression in normal tissues and relative expression of each PAX8 regulon upon knocking out the indicated genes.

Figure 1—figure supplement 3.

(A) Hierarchical clustering of PAX8 regulon gene expression in normal human tissues. (B) Relative expression of each PAX8 regulon gene upon knocking out the indicated members. (C) Relative expression of each PAX8 regulon gene upon knocking out PAX8 in the indicated cell lines.
Figure 1—figure supplement 4. Correlation estimation of PAX8 and each regulon gene in ovarian cancer cell lines and TCGA ovarian tumors.

Figure 1—figure supplement 4.

(A) Correlation estimation of PAX8 and each regulon gene at the mRNA level in ovarian cancer cell lines. (B) Correlation estimation of PAX8 and each regulon gene at the mRNA level in TCGA ovarian tumors.
Figure 1—figure supplement 5. Molecular subgroup analysis and prognosis analysis of PAX8 and PAX8 regulon signature.

Figure 1—figure supplement 5.

(A) Comparison of PAX8 regulon signature or PAX8 gene expression between indicated ovarian cancer subgroups. (B) Kaplan-Meier plots of overall survival (OS) or progression-free survival (PFS) in ovarian cancer patients stratified by PAX8 regulon signature or PAX8 gene expression levels.