Our study improves over previous studies in that it introduces circulating lncRNAs as novel complementary biomarkers in DLBCL diagnosis, prognosis and prediction of patient responsiveness to R-CHOP therapy. interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine. valueInternational Prognostic Index, lactate dehydrogenase, performance status. Patients were classified based on their end of Olaparib (AZD2281) study treatment response as shown in Fig.?1. After completion of the R-CHOP treatment cycles, DLBCL patients (n?=?84) were classified according to response evaluation criteria into complete responders (CR), n?=?38; partial responders (PR), n?=?21; and non-responders (NR), n?=?25. Thus, the overall responders (CR?+?PR) were 59/84 (70%), while the NR patients were 25/84 (30%). Comparison of the clinicopathological data of overall responder and NR groups revealed statistically significant higher IPI scores in NRs compared to the overall responders (complete response, partial response, nonresponders, number. Table 2 Clinical data of overall responders and non-responders to R-CHOP therapy. valueInternational Prognostic Index, lactate dehydrogenase, Olaparib (AZD2281) performance status. *Indicates statistical significance International Prognostic Index,?values and the results of Gene ontology (GO) and KEGG pathway analyses for each lncRNA-related PPI are listed in Table ?Table4.4. The lncRNA-related PPI network construction is usually visualized in Fig.?6. Table 4 Bioinformatics analysis of the lncRNAs-related genes and proteinCprotein interactions linked to drug responsiveness. value 0.05). Open in a separate window Physique 6 Construction of lncRNA-related PPI networks linked to Rabbit Polyclonal to ETV6 drug responsiveness in DLBCL. (A) HOTAIR, (B) GAS5, (C) XIST, (D) HOTAIR?+?GAS5. Pathway Studio online software Olaparib (AZD2281) was used. Discussion The pathogenesis of DLBCL involve multi-step and heterogeneous processes with different genetic and epigenetic changes, and that high epigenomic heterogeneity correlated with a higher relapse rate and poor outcome25,26. The lack of clear symptoms and early detection makes it difficult to diagnose at an early stage, leading to poor prognosis. Existing molecular prognostic markers of DLBCL include MYC, P53, BCL2, and Ki-67. However, they have several limitations. MYC and P53 mutations are found in only 10% and 15C30% of DLBCL patients, respectively27. BCL2 is usually upregulated in 40C60% of patients and is associated with worse outcomes only in certain subtypes of DLBCL, while data about Ki-67 were controversial27, necessitating the identification of new predictive markers. Recently, expectations have been raised regarding the potential role of lncRNAs as predictive markers28C30 and as potential mediators of resistance to cancer therapy31,32, however, these studies were carried out on tumor tissue samples and/or cell lines. Herein, we found that plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients indicating Olaparib (AZD2281) their involvement in the pathogenesis of DLBCL. To the best of our knowledge, we are the first to provide evidence about XIST expression in DLBCL and its diagnostic and prognostic significance. In addition, we exhibited that plasma levels of HOTAIR, GAS5 and XIST showed a discriminative ability for DLBCL, suggesting them as surrogate non-invasive biomarkers of DLBCL diagnosis, with GAS5 was of superior diagnostic performance. We also recorded that baseline plasma HOTAIR and GAS5 were associated with prognosis and therapy outcome, with HOTAIR exhibited predictive ability for R-CHOP failure. We also constructed the HOTAIR- and GAS5-related PPI networks to explore their role in drug response in DLBCL. Our results introduce GAS5 and HOTAIR as novel candidates for future large scale predictive studies in personalized medicine. First-line early.