**7. Bioinformatics analysis of retinoid signaling components in CRC**

We extended our study of RA signaling in CRC herein by using bioinformatics to analyze expression and mutation of RA signaling genes in CRCs and identify RA pathway genes that predict CRC patient survival. We found that most genes in the RA pathway are overexpressed and many are mutated in CRC (**Figure 2**). This is consonant with our previous result showing that RAR, RXR and other RA signaling proteins are overexpressed in CRC, which parallels overpopulation of ALDH-positive SCs that occurs during CRC tumorigenesis [39, 46]. Moreover, we found that aberrant expression of many RA signaling proteins (10 of 27) predicted (p < 0.05) decreased survival of CRC patients (**Figure 3**). We refer the reader to the meta-analysis by Chen et al. [63] which reveals that increased ALDH also indicates a poor prognosis in CRC patients. These updated findings provide insight into the complexity of RA signaling mechanisms and how RA signaling, when dysregulated, contributes to the development of CRC.

**Figure 2.**

*Bioinformatics analyses of RA signaling genes in CRC, including overexpression (a) and mutations (b). Bioinformatics data derived from cosmic catalog of somatic mutations in cancer (https://cancer.sanger.ac.uk/ cosmic).*
