背景:复发和转移是非小细胞肺癌(NSCLC)相关死亡的主要原因。CD146已被确定为不良预后的潜在危险因素,与多种肿瘤的远处转移和耐药密切相关。然而,CD146在NSCLC中的临床意义需要进一步研究.
方法:本研究使用从我们医院收集的肿瘤组织样本探索CD146表达与临床变量之间的相关性。CD146在NSCLC细胞系和组织中的表达水平进行了评估和比较,使用免疫组织化学,实时聚合酶链反应(RT-qPCR),流式细胞术,和蛋白质印迹分析。使用transwell和伤口愈合测定法确定肿瘤细胞的侵袭和迁移能力。通过蛋白质印迹法测量与上皮-间质转化(EMT)以及潜在的PI3K/Akt信号通路相关的蛋白质的水平。
结果:我们发现CD146表达与EMT信号通路显著相关。CD146高表达预测淋巴结转移,转移到远处器官,晚期肿瘤,节点,转移(TNM)分期,非小细胞肺癌患者生存率低。伤口愈合和transwell实验表明,敲除CD146显著抑制细胞迁移和细胞侵袭,而过度表达CD146显著增强了这些过程。Westernblot分析显示N-cadherin水平显著降低,波形蛋白,蜗牛,twist,PI3K,与载体对照细胞相比,shCD146H460细胞中的AKT磷酸化。PI3K抑制剂PI3K-IN-1治疗增加了E-cadherin表达水平,但减少了N-cadherin,Twist,Vimentin,PI3K,与载体对照细胞相比,pcDNA3.1-CD146A549细胞中的AKT磷酸化水平。
结论:CD146表达是NSCLC不良预后的危险因素,通过PI3K/Akt信号通路激活EMT促进侵袭和转移。这些发现强调了针对CD146的潜在治疗策略,为NSCLC患者提供了新的治疗选择。尤其是那些有转移风险的人。
BACKGROUND: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation.
METHODS: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting.
RESULTS: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells.
CONCLUSIONS: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.