Multiomic Characterization of <i>RCC1</i> and <i>RCC2</i> Expression and Their Association With Molecular Alterations, Immune Phenotypes, and Cancer Outcomes.

Abstract

Regulator of chromosome condensation 1 (<i>RCC1</i>) and <i>RCC2</i> have been shown to play important roles in the regulation of cell cycle, DNA damage response, and nucleocytoplasmic transport. DNA (592-gene or whole exome) and RNA (whole transcriptome) sequencing was performed at Caris Life Sciences (Phoenix, AZ). Samples were stratified by <i>RCC1</i> 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 (*<i>P</i> < .05). Corresponding analyses were run for <i>RCC2</i>. Median <i>RCC1</i> 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 <i>RCC1</i>, the median <i>RCC2</i> expressions were highest in SCLC (36.2 TPM). Tumor mutational burden-high rates were positively associated with increasing <i>RCC1</i> expression quartiles (Q1-4) in NSCLC (31%-41%), GC (7%-22%), and CRC (5%-17%) and with increasing <i>RCC2</i> expression in NSCLC and CRC only. Higher expression with <i>RCC1</i> and <i>RCC2</i> was associated with worse overall survival in NSCLC (hazard ratio [HR] for <i>RCC1</i> and <i>RCC2</i> were 1.3 and 1.3, respectively), PC (HR for <i>RCC1</i> and <i>RCC2</i> were 1.5 and 1.12, respectively), and CRC (HR for <i>RCC1</i> and <i>RCC2</i> were 1.3 and 1.03, respectively). <i>RCC1</i> and <i>RCC2</i> expression is a negative prognostic marker in NSCLC, PC, and CRC. Further studies to investigate <i>RCC1</i> and <i>RCC2</i> function at the molecular level may provide opportunities for novel targeted drug development.