A prospective study of the use of circulating markers as predictors for epidermal growth factor receptor-tyrosine kinase inhibitor treatment in pulmonary adenocarcinoma.
BACKGROUND
The use of liquid tissue, such as circulating cells, to predict treatment response is attracting more attention.


OBJECTIVE
The aim of this study was to evaluate association between circulating markers and treatment response.


METHODS
One hundred and twelve advanced pulmonary adenocarcinoma patients who were going to receive epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were included. Tumor tissue and plasma specimens were collected before treatment and analyzed for EGFR mutation and plasma IL-6 and IL-8. Pre-treatment peripheral blood CD146+/CD3- cells (as circulating endothelial cells, CECs), CD34+/CD45- cells (as endothelial progenitor cells, EPCs), and CD133+ cells (as cancer stem cells, CSCs) were measured with flow cytometry.


RESULTS
The progression-free survival (PFS) was significantly longer in patients with low CEC, low EPC, and low CSC counts than in those with high cell counts (p < 0.001, 0.041, and 0.001, respectively). Multivariate analysis showed that mutant plasma EGFR (pEGFR) was a poor prognostic factor in EGFR-mutated patients (p = 0.048), and there was a tendency for EGFR mutation-negative patients with high IL-6 level to have worse overall survival (p = 0.051).


CONCLUSIONS
CECs, EPCs, CSCs, and mutant pEGFR are useful predictive biomarkers of EGFR-TKI treatment efficacy. IL-6 may predict prognosis in advanced lung cancer.
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Yung-Hung
YH
Luo
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Pei-Chun
PC
Tseng
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Sijhih Cathay General Hospital, Taipei, Taiwan.
Yu-Chin
YC
Lee
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Reury-Perng
RP
Perng
Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
Jacqueline
J
Whang-Peng
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
Yuh-Min
YM
Chen
D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D004252:DNA Mutational Analysis; D042783:Endothelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
Adenocarcinoma; cancer stem cells; circulating endothelial cells; cytokines; endothelial progenitor cells; epidermal growth factor receptor (EGFR)