Non-coding RNAs are fundamental to the competing endogenous RNA (CeRNA) hypothesis in oncology. Previous work focused on static CeRNA networks. We construct and analyze CeRNA networks for four sequential stages of lung adenocarcinoma (LUAD) based on multi-omics data of long non-coding RNAs (lncRNAs), microRNAs and mRNAs. We find that the networks possess a two-level bipartite structure: common competing endogenous network (CCEN) composed of an invariant set of microRNAs over all the stages and stagedependent, unique competing endogenous networks (UCENs). A systematic enrichment analysis of the pathways of the mRNAs in CCEN reveals that they are strongly associated with cancer development. We also find that the microRNA-linked mRNAs from UCENs have a higher enrichment efficiency. A key finding is six microRNAs from CCEN that impact patient survival at all stages, and four microRNAs that affect the survival from a specific stage. The ten microRNAs can then serve as potential biomarkers and prognostic tools for LUAD.

Background: The treatment for stage IV non-small cell lung cancer relies on molecular diagnosis on tumor DNA for guiding systemic therapy. Liquid biopsy provides a timely and non-invasive way of detecting potential therapeutic targets and spares the need of performing a confirmatory biopsy procedure in patients with a positive result. Method: We report local experience on epidermal growth factor receptor (EGFR) mutations detected by two platforms (droplet digital polymerase chain reaction (ddPCR) technique and Cobas EGFR v2) on cell free tumor DNA from radiological stage IV lung cancer patients, guiding firstand second-generation EGFR tyrosine kinase inhibitor (TKI) therapy. All these patients who had either plasma EGFR platforms done from Nov 2015 to May 2017 are retrospectively identified and analyzed. Result: 97 patients identified. 11 out of 39 (28.2%) and 16 out of 58 (27.6%) has detectable EGFR mutation in plasma by using ddPCR and Cobas techniques respectively. Much higher detection rate is noted in never smokers (23/46, 50.0%) compared with chronic/ever smokers (4/41, 9.8%) and is highly statistically significant for difference (p-value: <0.001). The types of EGFR mutations detected are as follows: ddPCR method: 4 (36.4%) del 19, 7 (63.6%) L858R. Cobas method: 5 (31.3%) del 19, 9 (56.3%) L858R, 2 (12.5%) G719X. 20 (74.1%) patients were eventually put on 1st or 2nd EGFR-TKI as first line treatment and, among those, 17 (85%) attained partial response as the best treatment response and the median PFS and OS of is not reached. Among the 56 patients who obtained tissue biopsy/cytology along the course of disease, 6 (10.7%) of which carries histology (3 squamous cell carcinoma, 1 peripheral nerve sheath tumor, and 1 small cell carcinoma and 1 large cell tumor neuroendocrine tumor) that's not normally sent for EGFR molecular testing, as well as 11 (19.6%) patients having NSCLC-NOS histology only. Conclusion: ddPCR and Cobas EGFR v2 platforms have similar detection rate and chance of avoiding the need of a confirmatory tissue biopsy. A simple clinical history of smoking status determines the yield of a positive result. Plasma liquid biopsy provides a non-invasive and promising way for treatment initiation in radiological lung cancer.

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