MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case-control study.
BACKGROUND
Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample.


METHODS
A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis.


RESULTS
Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively.


CONCLUSIONS
A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool.
Division of Thoracic Surgery, Department of Surgery, University of Alberta, Edmonton, AB;
R
R
Razzak
Division of Thoracic Surgery, Department of Surgery, University of Alberta, Edmonton, AB;
E L R
EL
Bédard
Department of Radiation Oncology, CancerCare Manitoba, and University of Manitoba, Winnipeg, MB;
J O
JO
Kim
Division of Thoracic Surgery, Department of Surgery, University of Alberta, Edmonton, AB;
S
S
Gazala
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB;
L
L
Guo
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB;
S
S
Ghosh
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB;
A
A
Joy
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB;
T
T
Nijjar
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB;
E
E
Wong
Division of Pulmonary Medicine, Department of Internal Medicine, University of Alberta Hospital and University of Alberta, Edmonton, AB.
W H
WH
Roa
Non-small-cell lung cancer; mirna; nsclc; rt-pcr; screening; sputum