背景:贝沙罗汀,也被公认为Targretin,被归类为类视色素,一种抗癌药物。然而,贝沙罗汀与结肠癌相关的确切机制尚不清楚.在结肠癌中,SEZ6L2被认为是生物标志物和靶标之一。本研讨对SEZ6L2在结肠癌中的感化停止了周全的摸索。
方法:我们利用了TCGA数据和中国患者队列。在对478例结肠癌病例的细致分析中,检查SEZ6L2表达水平与临床特征的关系,暂存参数,和治疗结果。此外,我们研究了贝沙罗汀对SEZ6L2的药理作用,证实了贝沙罗汀治疗后结肠癌患者SEZ6L2的mRNA和蛋白水平均显著下调.
结果:SEZ6L2在结肠癌中持续过度表达,作为具有预后意义的潜在通用生物标志物,在不同的中国队列中验证。体外,SEZ6L2促进细胞活力而不影响迁移。贝沙罗汀治疗抑制SEZ6L2表达,与体外和体内活力降低相关。在体内背景下,SEZ6L2过表达加速存活率下降。贝沙罗汀的功效取决于上下文,对亲代细胞有效,但对SEZ6L2过表达无效。计算预测表明SEZ6L2-贝沙罗汀存在直接相互作用,值得进一步的实验探索。
结论:该研究为SEZ6L2作为结肠癌预后生物标志物提供了有价值的见解,揭示了它与临床参数的复杂关系,治疗结果,和贝沙罗汀的作用。上下文相关的治疗反应强调SEZ6L2在结肠癌中的作用所需的细微差别的理解,为有针对性的治疗策略铺平道路。
BACKGROUND: Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of
bexarotene in relation to colon cancer remain unclear. In colon cancer, SEZ6L2 was suggested as one of the biomarkers and targets. This study presents a comprehensive exploration of the role of SEZ6L2 in colon cancer.
METHODS: We utilized both TCGA data and a cohort of Chinese patients. In a meticulous analysis of 478 colon cancer cases, SEZ6L2 expression levels were examined in relation to clinical characteristics, staging parameters, and treatment outcomes. Additionally, we investigated the pharmacological impact of bexarotene on SEZ6L2, demonstrating a significant downregulation of SEZ6L2 at both mRNA and protein levels in colon cancer patients following
bexarotene treatment.
RESULTS: SEZ6L2 consistently overexpresses in colon cancer, serving as a potential universal biomarker with prognostic significance, validated in a diverse Chinese cohort. In vitro, SEZ6L2 promotes cell viability without affecting migration.
Bexarotene treatment inhibits SEZ6L2 expression, correlating with reduced viability both in vitro and in vivo. SEZ6L2 overexpression accelerates declining survival rates in an in vivo context. Bexarotene\'s efficacy is context-dependent, effective in parental cells but not with SEZ6L2 overexpression. Computational predictions suggest a direct SEZ6L2-
bexarotene interaction, warranting further experimental exploration.
CONCLUSIONS: The study provides valuable insights into SEZ6L2 as a prognostic biomarker in colon cancer, revealing its intricate relationship with clinical parameters, treatment outcomes, and bexarotene effects. Context-dependent therapeutic responses emphasize the nuanced understanding required for SEZ6L2\'s role in colon cancer, paving the way for targeted therapeutic strategies.