Wu Chia-Ming, Chen Chung-Hsing, Tsai Kuo-Wang, Tan Mei-Chen, Tsai Fang-Yu, Jiang Shih-Sheng, Chen Shang-Hung, Chen Wei-Shone, Wang Horng-Dar, Huang Tze-Sing
Graduate Program of Biotechnology in Medicine, National Health Research Institutes, National Tsing Hua University, Hsinchu City 300, Taiwan.
Institute of Biotechnology, National Tsing Hua University, Hsinchu City 300, Taiwan.
Cells. 2024 Dec 10;13(24):2035. doi: 10.3390/cells13242035.
Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12-MALAT1 alliance is linked to poorer prognosis independently of age and metastasis. To identify the downstream effects responsible for this outcome, we analyzed 2312 common target genes of TCF12 and MALAT1, finding involvement in pathways like Aurora B, ATM, PLK1, and non-canonical WNT. We investigated the impact of WNT downstream genes and , encoding β-catenin and cyclin D1, respectively, on survival in CRC patients with this alliance. Tumors with higher and gene expressions alongside increased gene expressions were classified as having a "Pan-CMS-2 pattern", showing relatively better prognoses. Conversely, tumors with high , , and gene expressions but low expression were categorized as "TMBC pattern", associated with poor survival, with survival rates dropping sharply from 60% at one year to 30% at three years. This suggests that targeting cyclin D1-associated CDK4/6 could potentially reduce early mortality risks in TMBC patients, supporting personalized medicine approaches.
转移是一个众所周知的会恶化结直肠癌（CRC）预后的因素，但对于非转移性且预后较差的患者的死亡机制了解较少。TCF12是一种转录因子，它可以与长链非编码RNA MALAT1发生物理关联，在CRC患者中形成具有相关表达水平的联盟。这种TCF12-MALAT1联盟与较差的预后相关，且与年龄和转移无关。为了确定导致这一结果的下游效应，我们分析了TCF12和MALAT1的2312个共同靶基因，发现它们参与了诸如Aurora B、ATM、PLK1和非经典WNT等信号通路。我们研究了分别编码β-连环蛋白和细胞周期蛋白D1的WNT下游基因和对具有这种联盟的CRC患者生存的影响。具有较高和基因表达以及增加的基因表达的肿瘤被归类为具有“泛CMS-2模式”，显示出相对较好的预后。相反，具有高、和基因表达但低表达的肿瘤被归类为“TMBC模式”，与较差的生存率相关，生存率从一年时的60%急剧下降到三年时的30%。这表明靶向细胞周期蛋白D1相关的CDK4/6可能会降低TMBC患者的早期死亡风险，支持个性化医疗方法。
