Post-Surgery Circulating Tumor Cells and AXL Overexpression as New Poor Prognostic Biomarkers in Resected Lung Adenocarcinoma
Post-Surgery Circulating Tumor Cells and AXL Overexpression as New Poor Prognostic Biomarkers in Resected Lung Adenocarcinoma
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DOI：
10.3390/cancers11111750
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发表时间：
2019-11-01
期刊：
影响因子：
5.2
通讯作者：
Jose Serrano, Maria
中科院分区：
文献类型：
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作者：
de Miguel-Perez, Diego;Isabel Bayarri-Lara, Clara;Jose Serrano, Maria
背景：早期非小细胞肺癌(NSCLC)的预后相当令人失望，辅助治疗的益处相对较小。因此，迫切需要确定新的预测和预测生物标记物。肺腺癌具有明显的临床病理特征，新的治疗策略正在积极评估中。在这里，我们研究了循环肿瘤细胞(CTCs)以及基因和miRNA组织表达对可切除非小细胞肺癌预后的影响。患者和方法：与鳞状细胞癌(SCC)相比，我们评估了早期肺腺癌(ADC)切除患者在三个不同时间点(CTC1-3)(手术前、术后1个月和术后6个月)的CTC亚群与预后的关系。此外，基因和miRNA组织表达、免疫图谱和上皮向间充质转化(EMT)标记物与预后相关。结果：ADC(n=47)和SCC(n=50)表现出不同的组织表达谱，导致存在不同的CTC亚群。在ADC中，miR155与Ax1和IL6R的表达呈正相关，与EMT CTc1的表达呈正相关(p=0.014和p=0.004)。在多因素分析中，CTC2是无复发生存的独立预后因素，CTC3和Ax1是仅在ADC中影响总体生存的独立预后因素。手术和辅助治疗均不影响患者的预后。结论：我们的研究阐明了腺癌患者术后组织Axl的表达和CTCs的存在对预后的影响。组织Axl表达和CTC EMT激活可能是ADC患者分层的潜在生物标志物，可能受益于新的辅助治疗。
Background: The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. Thus, there is an urgent need to identify novel prognostic and predictive biomarkers. Lung adenocarcinoma has distinct clinical-pathological characteristics and novel therapeutic strategies are under active evaluation in the adjuvant setting. Here, we investigated the prognostic impact of circulating tumor cells (CTCs) and gene and miRNA tissue expression in resectable NSCLC. Patients and methods: We assessed the association between CTC subpopulations and the outcome of resected early stage lung adenocarcinoma (ADC) patients at three different time-points (CTC1-3) (before surgery, after one month, and after six months) in comparison to squamous cell carcinoma (SCC). Furthermore, gene and miRNA tissue expression, immunoprofiling, and epithelial-to-mesenchymal transition (EMT) markers were correlated with outcome. Results: ADC (n = 47) and SCC (n = 50) revealed different tissue expression profiles, resulting in the presence of different CTC subpopulations. In ADC, miR-155 correlated with AXL and IL6R expression, which were related to the presence of EMT CTC1 (p = 0.014 and p = 0.004). In the multivariate analysis, CTC2 was an independent prognostic factor for relapse-free survival, and CTC3 and AXL were independent prognostic for overall survival only in ADC. Neither the surgery nor the adjuvant treatment influenced the prognosis of these patients. Conclusions: Our study elucidate the prognostic impact of tissue AXL expression and the presence of CTCs after surgery in adenocarcinoma patients. Tissue AXL expression and CTC EMT activation could potentially represent biomarkers for the stratification of ADC patients that might benefit from new adjuvant therapies.