Abstract
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.
Highlights
The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small
We found that higher expression of IL6R, AXL, and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) correlated with the presence of epithelial-to-mesenchymal transition (EMT) + CTC1 in these patients (p = 0.004, p = 0.014, and p = 0.021, respectively) (Figure 2B)
We reported that the presence of heterogeneous circulating tumor cells (CTCs) subpopulations is associated with tissue-specific genetic and miRNAs profiles in resected lung adenocarcinoma and how the role of the combination of both factors can identify patients with shorter relapse-free survival (RFS) and overall survival (OS)
Summary
The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. 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). SCC patients have lower survival rates after surgery [5] These differences might be explained by the tumor mutation burden (TMB), as high nonsynonymous TMB was a favorable prognostic factor in resected NSCLC [6]. Despite the increasing knowledge about the biological behavior of these subtypes, the differences in the aggressiveness pattern between SCC and ADC are not clear yet
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