Abstract
Background: Lung cancer is the second most common cancer and the main leading cause of cancer-associated death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer diagnoses and more than 50% of all lung cancer cases are diagnosed at an advanced stage; hence have poor prognosis. Therefore, it is important to diagnose NSCLC patients reliably and as early as possible in order to reduce the risk of mortality. Methods: We identified blood-based gene markers for early NSCLC by performing a multi-omics approach utilizing integrated analysis of global gene expression and copy number alterations of NSCLC patients using array-based techniques. We also validated the diagnostic and the prognostic potential of the gene signature using independent datasets with detailed clinical information. Results: We identified 12 genes that are significantly expressed in NSCLC patients’ blood, at the earliest stages of the disease, and associated with a poor disease outcome. We then validated 12-gene signature’s diagnostic and prognostic value using independent datasets of gene expression profiling of over 1000 NSCLC patients. Indeed, 12-gene signature predicted disease outcome independently of other clinical factors in multivariate regression analysis (HR = 2.64, 95% CI = 1.72–4.07; p = 1.3 × 10−8). Significantly altered functions, pathways, and gene networks revealed alterations in several key genes and cancer-related pathways that may have importance for NSCLC transformation, including FAM83A, ZNF696, UBE2C, RECK, TIMM50, GEMIN7, and XPO5. Conclusion: Our findings suggest that integrated genomic and network analyses may provide a reliable approach to identify genes that are associated with NSCLC, and lead to improved diagnosis detecting the disease in early stages in patients’ blood instead of using invasive techniques and also have prognostic potential for discriminating high-risk patients from the low-risk ones.
Highlights
Despite the advances in cancer therapies and raising awareness, lung cancer continues to be one of the most malignant tumors
The poor outcome of many Non-smallcell lung carcinoma (NSCLC) patients stems from the fact that many are diagnosed after their cancer has developed into advanced stages (Xie and Xie, 2019; Chen et al, 2020), further indicating the necessity of identifying NSCLC at an early stage for maximizing patient survival
We downloaded RNAseq dataset for NSCLC patients from The Cancer Genome Atlas (TCGA) that contains 576 samples (n = 517 tumor, 279 of which are with Stage 1 and 59 normal samples)
Summary
Despite the advances in cancer therapies and raising awareness, lung cancer continues to be one of the most malignant tumors. It is the second most common cancer and the leading cause of cancer-related death worldwide (Bray et al, 2018). Recent genomic studies have shown that changes in gene expression and copy number variants (CNVs) have been associated with human diseases, including cancer (Colak et al, 2010; Colak et al, 2013), and identified potential biomarkers for the disease using RNA- or DNA-based approaches (Jabs et al, 2017; Chakraborty et al, 2018). It is important to diagnose NSCLC patients reliably and as early as possible in order to reduce the risk of mortality
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.
