Nagasaka Misako, Warnecke Brian, Ou Sai-Hong Ignatius, Bannoura Sahar F, Kim Chul, Elliott Andrew, Halmos Balazs, Hoon Dave, Darabi Sourat, Sukari Ammar, Radovich Milan, Lou Emil, Sledge George, El-Deiry Wafik, Al-Hallak Mohammed Najeeb, Pasche Boris C, Azmi Asfar S
University of California Irvine, Orange, CA.
St Marianna University School of Medicine, Kawasaki City, Kanagawa, Japan.
JCO Oncol Adv. 2025 May 1;2(1):00022. doi: 10.1200/OA-24-00033. eCollection 2025.
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.
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 .
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).
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.
染色体凝聚调节因子1（）和已被证明在细胞周期调控、DNA损伤反应及核质运输中发挥重要作用。
在Caris生命科学公司（亚利桑那州凤凰城）进行DNA（592基因或全外显子组）和RNA（全转录组）测序。对小细胞肺癌（SCLC；n = 876）、非小细胞肺癌（NSCLC；n = 21,603）、胃癌（GC；n = 1,908）、胰腺癌（PC；n = 5,071）和结直肠癌（CRC；n = 14,892）样本，根据表达四分位数阈值（Q1：低，Q4：高）进行分层。使用卡方检验和Wilcoxon秩和检验确定统计学显著性，并针对多重比较进行校正（* <.05）。对进行了相应分析。
SCLC中染色体凝聚调节因子1 mRNA表达中位数最高（每百万转录本[TPM]为14.3），其次是GC（9.9）、NSCLC（9.9）、CRC（9.8）和PC（6.9）。与染色体凝聚调节因子1相似，SCLC中的中位数表达最高（36.2 TPM）。肿瘤突变负荷高发生率与NSCLC（31%-41%）、GC（7%-22%）和CRC（5%-17%）中染色体凝聚调节因子1表达四分位数增加（Q1 - 4）呈正相关，且仅与NSCLC和CRC中染色体凝聚调节因子1表达增加相关。染色体凝聚调节因子1和表达较高与NSCLC（染色体凝聚调节因子1和的风险比[HR]分别为1.3和1.3）、PC（染色体凝聚调节因子1和的HR分别为1.5和1.12）及CRC（染色体凝聚调节因子1和的HR分别为1.3和1.03）的总生存期较差相关。
染色体凝聚调节因子1和表达是NSCLC、PC和CRC的不良预后标志物。进一步在分子水平研究染色体凝聚调节因子1和功能可能为新型靶向药物开发提供机会。
