Abstract
Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients.
Highlights
The continuous search for tumor markers has yielded several positive results [1]
The identification of molecular subtypes of non-small cell lung carcinoma (NSCLC) has transformed the clinical management of this disease, which is best exemplified by the clinical success of targeting the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) with tyrosine kinase inhibitors (TKI) as the first line of treatment [2]
Expression Level of cytokeratin 7 (CK7), E74-like factor 3 (ELF3), EGFR, and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) mRNA in NSCLC Tissues
Summary
Research on biomarkers playing a vital role in the early diagnosis and individualized treatments of the tumors is rapidly advancing as we begin to understand the complex mechanisms during tumor carcinogenesis and progression [1]. The identification of molecular subtypes of non-small cell lung carcinoma (NSCLC) has transformed the clinical management of this disease, which is best exemplified by the clinical success of targeting the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) with tyrosine kinase inhibitors (TKI) as the first line of treatment [2]. Lung cancer is still the leading cause of cancer mortality worldwide. The high mortality is due to the poor prognosis of the disease caused by late presentation of illness, tumor heterogeneities within histological subtypes, and the limited understanding of tumor biology. Invasive biomarkers present in sputum, plasma, serum, or whole blood have increasingly been explored for the early diagnosis of NSCLC
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