Over- and under-expressed genes are highlighted in WNT signaling pathway.

The KEGG pathway map for the human WNT signaling pathway (hsa 04310) was illustrated using the KEGG Mapper; genes correlated with RSPO3 expression are colored in pink.</p

Gene expression heatmap of 7 cancer-related pathways enriched with genes that were correlated to RSPO3 in RNA expression.

A total of 256 genes associated with Apoptosis, Direct p53, EGFR, ErbB, SCF-KIT, VEGFR, WNT signaling showed significant differences in expression between RSPO3 fusion-positive colorectal samples and the control samples (see details in Methods). The RNA expression was transformed to z-score. The x-axis represents the sample, and the y-axis represents the RNA expression.</p

Putative target genes involved in multiple pathways of PTPRK-RSPO3 fusion-positive cancer.

(PDF)</p

Putative target genes and actionable drugs involved in ten major cancer-related pathways.

(XLSX)</p

Clinicopathological characteristics of <i>PTPRK-RSPO3</i> fusion-positive and fusion-negative cases in TCGA colorectal cancer.

Clinicopathological characteristics of PTPRK-RSPO3 fusion-positive and fusion-negative cases in TCGA colorectal cancer.</p

2,505 genes correlated with RSPO3 (R >0.2).

(XLSX)</p

Overall design of this study.

Transcriptome data for colorectal cancer (CRC) was attained from the Broad GDAC Firehose database. Following the RNA expression analysis of a total of 20,531 genes, 2,505 genes correlated with RSPO3 expression were selected. (R-value > 0.2, see Methods). Over-representation analysis of the 2,505 genes showed significant relation to 10 major cancer-related pathways (Apoptosis Related Pathway, Direct p53 Related Pathway, EGFR Related Pathway, ErbB Related Pathway, JAK-STAT Related Pathway, JAK-STAT Related Pathway, Tyrosine Kinases Related Pathway, Pathways in Cancer, SCF-KIT Related Pathway, VEGFR Related Pathway, WNT Related Pathway). Potential targets and repurposed drugs were inferred by analyzing target-drug associations via literature reviews and network analysis using the differentially expressed gene list and target-drug databases.</p

Inferred drug-target network in PTPRK-RSPO3 fusion-positive colorectal cancer.

Drug-target relation was obtained based on CIViC and OncoKB databases: White boxes, drugs; circles, underlined white boxes, substitute drugs; genes; red circles, genes that are over-expressed in fusion-positive cancer; blue circles, genes that are under-expressed in fusion-positive cancer. The red lines are prioritized drug-target relationships based on the scenario that properly working cancer drugs are generally inhibitors for activated oncogenes or activators for down-regulated tumor suppressor genes.</p

Inferred drug-target network in PTPRK-RSPO3 fusion-positive colorectal cancer based on VICC database.

(PDF)</p

The KEGG pathway maps for the human ERBB signaling pathway and pathways in cancer using the KEGG Mapper; genes correlated with RSPO3 expression are colored in pink.

(PDF)</p