Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma.
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 ofCK7andELF3in tumor tissues andEGFRin PBMCs was associated with lymph node metastasis (allp< 0.05). The expression ofCK7in PBMCs was correlated with age andEphB4in PBMCs correlated with histopathological type, respectively (allp< 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (allp< 0.01). Survival analysis showed that the patients with enhanced expression ofCK7,ELF3,EGFR, andEphB4mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (allp< 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.
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. yuxinmin19750705@outlook.com.|Department of Thoracic Tumor Chemotherapy, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. yuxinmin19750705@outlook.com.|Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou 310022, China. yuxinmin19750705@outlook.com.
Xin-Min
XM
Yu
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. wuyichen19870807@hotmail.com.
Yi-Chen
YC
Wu
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. liuxiang19880808@outlook.com.
Xiang
X
Liu
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. huangxiancong@hotmail.com.
Xian-Cong
XC
Huang
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. houxiuxiu@hotmail.com.
Xiu-Xiu
XX
Hou
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. wangjl1988@outlook.com.
Jiu-Li
JL
Wang
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. chen_xiangliu@outlook.com.
Xiang-Liu
XL
Cheng
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. maowm88@outlook.com.|Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou 310022, China. maowm88@outlook.com.
Wei-Min
WM
Mao
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China. lingzq@zjcc.org.cn.|Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou 310022, China. lingzq@zjcc.org.cn.
Zhi-Qiang
ZQ
Ling
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics*; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D053552:Keratin-7 / Q000097:blood / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D036224:Receptor, EphB4 / Q000097:blood / Q000235:genetics*; D016019:Survival Analysis; D014157:Transcription Factors / Q000097:blood / Q000235:genetics*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D053552:Keratin-7; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; D036224:Receptor, EphB4
cell-free RNA content; circulating tumor cells (CTCs); non-small-cell lung carcinoma (NSCLC); peripheral blood mononuclear cells (PBMCs); prognosis