Multiomic Characterization of and Expression and Their Association With Molecular Alterations, Immune Phenotypes, and Cancer Outcomes.

PURPOSE

Regulator of chromosome condensation 1 () and have been shown to play important roles in the regulation of cell cycle, DNA damage response, and nucleocytoplasmic transport.

MATERIALS AND METHODS

DNA (592-gene or whole exome) and RNA (whole transcriptome) sequencing was performed at Caris Life Sciences (Phoenix, AZ). Samples were stratified by expression quartile thresholds (Q1: low, Q4: high) for small cell lung cancer (SCLC; n = 876), non-small cell lung cancer (NSCLC; n = 21,603), gastric cancer (GC; n = 1,908), pancreatic cancer (PC; n = 5,071), and colorectal cancer (CRC; n = 14,892). Statistical significance was determined using chi-square and Wilcoxon rank-sum tests and adjusted for multiple comparisons (* < .05). Corresponding analyses were run for .

RESULTS

Median mRNA expression was highest in SCLC (14.3 transcript per million [TPM]), followed by GC (9.9), NSCLC (9.9), CRC (9.8), and PC (6.9). Similar to , the median expressions were highest in SCLC (36.2 TPM). Tumor mutational burden-high rates were positively associated with increasing expression quartiles (Q1-4) in NSCLC (31%-41%), GC (7%-22%), and CRC (5%-17%) and with increasing expression in NSCLC and CRC only. Higher expression with and was associated with worse overall survival in NSCLC (hazard ratio [HR] for and were 1.3 and 1.3, respectively), PC (HR for and were 1.5 and 1.12, respectively), and CRC (HR for and were 1.3 and 1.03, respectively).

CONCLUSION

and expression is a negative prognostic marker in NSCLC, PC, and CRC. Further studies to investigate and function at the molecular level may provide opportunities for novel targeted drug development.