The mutational and transcriptional status of RYR in CRC and its indication for prognosis.

Aberrant calcium signaling, particularly the ryanodine receptor (RYR) signaling, is linked to cancer development. Currently, little is known about the status of RYR in colorectal cancer (CRC), and the correlation of RYR with CRC phenotypes remains unclear. We analyzed genetic alterations in RYRs using data from 587 patients with CRC in the TCGA database. Mutations were spread across RYR channels without identified hotspot mutations. RYR2 exhibited the highest mutation frequency (59%), with mutually exclusive mutations between RYR2 and RYR1/RYR3. RYR2 revealed significantly elevated transcription in CRC tissues, while RYR1 and RYR3 revealed decreased transcription. Patients with RYR mutations had higher tumor mutational burden (TMB). Stage-related differences in RYR1 and RYR2 transcription were detected. Although age was correlated with RYR1 mutation status, no significant differences in age or BMI were found between patients with low and high RYR transcription. Age, clinical stage, and tumor location were identified as prognostic factors, with age, clinical stage, and location being independent risk factors. In conclusion, RYRs exhibited variable mutational and transcriptional profiles in CRC, with RYR2 revealing unique patterns. Age, clinical stage, and tumor location represent independent risk factors in CRC with RYR mutations.