Circulating MicroRNAs as Minimally Invasive Biomarkers for Cancer Theragnosis and Prognosis

Novel cancer biomarker discovery is urgently needed for cancer theragnosis and prognosis, and among the many possible types of samples, blood is regarded to be ideal for this discovery as it can be collected easily in a minimally invasive manner. Results of the past few years have ascertained the quantification of microRNA (miRNA) as a promising approach for the detection and prognostication of cancer. Indeed, an increasing number of studies have shown that circulating cancer-associated miRNAs are readily measured in plasma or serum and they can robustly discriminate cancer patients from healthy controls, as well as distinguishing between good-prognosis and poor-prognosis patients. Furthermore, recent findings also suggest the potential of circulating miRNAs in the screening, monitoring, and treatment of cancer. This article summarizes the most significant and latest discoveries of original researches on circulating miRNAs involvement in cancer, focusing on the potential of circulating miRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis

Circulating Plasma MicroRNAs As Diagnostic Markers for NSCLC

Lung cancer is the most common cause of cancer deaths all over the world, in which non-small cell lung cancer (NSCLC) accounts for ~85% of cases. It is well known that microRNAs (miRNAs) play a critical role in various cellular processes, mediating post-transcriptional silencing either by mRNA degradation through binding the 3' UTR of target mRNA or by translational inhibition of the protein. In the past decade, miRNAs have also been increasingly identified in biological fluids such as human serum or plasma known as circulating or cell-free miRNAs, and may function as non-invasive diagnostic markers for various cancer types including NSCLC. Circulating tumor cells (CTCs) are those cells that are shed from solid tumors and then migrate into the circulation. However, reports concerning the roles of CTCs are quite rare, which may be attributed to the difficulties in the enrichment and detection of CTCs in the circulation. Although, there have been reassuring advances in identifying circulating miRNA-panels, which are assumed to be of diagnostic value in NSCLC early stage, some issues remain concerning the reliability of using miRNA panels as a diagnostic tool for NSCLC. In the current review, we are aiming at providing insights into the miRNAs biology, the mechanisms of miRNAs release into the bloodstream, cell-free miRNAs as the diagnostic markers for NSCLC and the current limitations of CTCs as diagnostic markers in NSCLC.Department of Health Technology and Informatic

Implications of MicroRNAs in the treatment of gefitinib-resistant non-small cell lung cancer

2015-2016 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Gene network exploration of crosstalk between apoptosis and autophagy in chronic myelogenous leukemia

Copyright © 2015 Fengfeng Wang et al. Background. Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear. Results. Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks. Conclusion. The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.Link_to_subscribed_fulltex

Role of Survival Post-Progression in Phase III Trials of Systemic Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Systematic Review

BACKGROUND: In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS). METHODS AND FINDINGS: Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r(2)) to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001) in parallel to the increase in MST (11.253-day increase per year; p<0.001); MPFS improved little (1.863-day increase per year). Overall, a stronger association was observed between MST and SPP (r(2) = 0.8917) than MST and MPFS time (r(2) = 0.2563), suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r(2) = 0.4428, 0.7242, and 0.9081 in 1988-1994, 1995-2001, and 2002-2007, respectively). CONCLUSIONS: SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials