Abstract
Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73–0.91), sensitivity of 100% (95% CI; 0.93–1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results.
Highlights
Lung cancer is the leading cause of cancer-related mortality world-wide, and was responsible for 1.38 million deaths in 2008 [1]
In an effort to develop non-invasive biomarker assays that can be used for early detection of lung cancer, we evaluated the expression of miRNA extracted from serum obtained from pretreatment Non small cell lung cancer (NSCLC) patients and cancer-free healthy subjects, to identify miRNA-based biomarkers that are capable of distinguishing between these groups
The demographic characteristics of the 30 NSCLC patients and 20 healthy patients with no history of cancer are shown in Figure 1 and Table 1
Summary
Lung cancer is the leading cause of cancer-related mortality world-wide, and was responsible for 1.38 million deaths in 2008 [1]. A metaanalysis of 7 lung cancer screening studies evaluated low dose helical CT scanning as a screening test for lung cancer and found that 14–55% of high-risk patients, with age $40 and $20 pack year smoking history, who had a suspicious lung lesion on a screening CT were found to have benign lung lesions after undergoing an invasive procedure for tissue diagnosis [13]. This high rate of invasive procedures for benign disease underscores the necessity for additional screening modalities that can potentially reduce the number of patients who undergo invasive procedures unnecessarily
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
