PO.MCB07.04 · 分子与细胞生物学
MYB表达在胰腺癌中逐步增加,与肿瘤分级进展、转移及患者不良生存相关
MYB expression increases progressively in pancreatic cancer, correlating with advancing tumor grade, metastasis, and poor patient survival
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摘要 Abstract
中文摘要
转录因子MYB在调控细胞增殖、分化和存活中发挥关键作用。尽管其在一部分胰腺癌中发生扩增,但新出现的证据表明MYB过表达也可能通过多种调控机制产生。我们此前已证明MYB在胰腺癌发病机制中的多种致癌作用;然而,其失调在肿瘤进展过程中的时间动态仍知之甚少。在此,我们通过免疫组织化学分析,研究了代表胰腺正常、癌前和恶性阶段的一系列组织样本以及配对肝转移中的MYB表达。使用适当的统计分析评估了MYB的差异表达及其与肿瘤分级进展和患者生存的相关性。我们观察到正常胰腺中MYB表达极微,其异常表达在癌前病变中开始显现,并随疾病进展逐步增加。转移病灶中也报告了MYB的高表达。MYB水平升高与更高的肿瘤分级呈正相关,并与胰腺癌患者生存缩短显著相关。有趣的是,对MYB过表达所调控基因的功能富集分析提示其参与关键致癌程序,包括增殖、存活、上皮-间质转化和转移信号通路。这些发现表明MYB失调在胰腺肿瘤发生早期即已出现并随疾病进展加剧,凸显其作为肿瘤侵袭性生物标志物及潜在治疗干预靶点的潜力。
查看英文原文 English abstract
The transcription factor MYB plays a pivotal role in regulating cell proliferation, differentiation, and survival. Although it is amplified in a subset of pancreatic cancers, emerging evidence indicates that MYB overexpression may also arise through diverse regulatory mechanisms. We have previously demonstrated multiple oncogenic roles of MYB in pancreatic cancer pathogenesis; however, the temporal dynamics of its dysregulation during tumor progression remain poorly understood. Here, we investigated MYB expression across a spectrum of tissue samples representing normal, precancerous, and malignant stages of the pancreas, as well as matched liver metastases, by performing immunohistochemical analysis. The differential expression of MYB and its correlation with advancing tumor grade and patient survival were assessed using appropriate statistical analyses. We observed negligible expression of MYB in the normal pancreas, and its aberrant expression became noticeable in precancerous lesions, increasing progressively as the disease advanced. A high expression of MYB was also reported in metastatic lesions. Elevated MYB levels were positively correlated with higher tumor grade and significantly associated with reduced survival of pancreatic cancer patients. Interestingly, functional enrichment analyses of genes regulated by MYB overexpression suggested its involvement in key oncogenic programs, including proliferation, survival, epithelial-mesenchymal transition, and metastatic signaling pathways. These findings demonstrate that MYB dysregulation occurs early in pancreatic tumorigenesis and intensifies with disease progression, underscoring its potential as a biomarker for tumor aggressiveness and a potential target for therapeutic intervention.
利益披露 Disclosure
S. Anand, None..
K. Vikramdeo, None..
M. Khan, None..
L. Xian, None..
P. M. Grandgenett, None..
J. E. Carter, None..
M. Khushman, None..
S. Singh, None..
A. Singh, None.