Title:Liquid Biopsy as Surrogate to Tissue in Lung Cancer for Molecular Profiling: A Meta-analysis
VOLUME: 14 ISSUE: 1
Author(s):Mona Mlika*, Chadli Dziri, Mohamed Majdi Zorgati, Mehdi Ben Khelil and Faouzi Mezni
Affiliation:Department of Pathology, Abderrahman Mami Hospital, Ariana, University Tunis El Manar, Faculty of Medicine of Tunis, Tunis, Medical Center of ABM, Military College, Department of Pathology, Abderrahman Mami Hospital, Ariana, Department of Pathology, Abderrahman Mami Hospital, Ariana
Keywords:Specific liquid biopsy, cfDNA, tissue, sensitivity, specificity, lung cancer.
Abstract:Background: The accurate microscopic diagnosis of lung cancer has become insufficient
due to the concept of personalized medicine. Tissue samples are used not only for microscopic diagnosis
but also for the assessment of the different targets. Biopsies are performed in 80% of the patients and
they are not sufficient for molecular diagnosis in 30 % of the cases. Liquid biopsy (LB) has been
reported as a possible surrogate to tissue samples and has been introduced in the management scheme
of the patients since 2014. We aimed to highlight the diagnostic value of liquid biopsy in assessing the
molecular profile of non small cell carcinomas in comparison with tissue biopsy.
Methods: We retracted eligible articles from PubMed, Embase and Cochrane databases. We
calculated the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative
likelihood ratio (NLR) and diagnostic odds ratio (DOR). A summary receiver operating characteristic
curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance
using the Meta-Disc software 5.1.32. The heterogeneity was assessed using I square statistics. A metaregression
was performed in case of heterogeneity. In case of absence of covariates, a sensitivity
analysis was done in order to assess publications that induced a statistical bias.
Results: 39 eligible studies involving 4782 patients were included. The overall statistical studies
showed heterogeneity in the SEN, SPE, PLR, NLR and DOR. No threshold effect was revealed. The
meta-regression incorporating the ethnicity, the test, the technique used in tissue and plasma and the
use of plasma or serum as covariates showed no impact of these factors. A sensitivity analysis allowed
achieving the homogeneity in the SPE and DOR. The overall pooled SEN and SPE were 0.61 and
0.95 respectively. The PLR was 9.51, the NLR was 0.45 and DOR was 24.58. The SROC curve with
AUC of 0,93 indicated that the liquid biopsy is capable of identifying wild type samples from mutated
ones with a relatively high accuracy.
Conclusion: This meta-analysis suggested that detection of molecular mutations by cfDNA is of
adequate diagnostic accuracy in association to tissues. The high specificity and the moderate
sensitivity highlight the value of LB as a screening test.
