Value for Both of Untreated to Treated Average Value for Both of Untreated Average Value for Both of Treated Pearson correlation doi:10.1371/journal.pone.0055520.t003 20.351 20.028 0.301 levels among those MedChemExpress Lck Inhibitor patients with stable disease versus those with progressive and mixed responses, be a good biomarker for CSCs when using protein assay. However, peripheral blood CD133 mRNA level reflected the amount of circulating CD133 positive cells, which often harbors KIT exon 11 mutation representing poor prognosis 16522807 and chemoresistant entity, might be a good marker for clinical application. Despite the lack of specific cellular entity of CD133+ cells, their rarity and functional diversity in the peripheral blood argues for the use of RT-PCR assays as primary means of detection which hold certain advantages over flow cytometry or circulating tumor cell technology. Paired samples size and large pre- and post treatment readouts difference in part compensated for the limited sample size in the current study. Low level of CD133 mRNA levels as observed in prolonged imatinib exposed patients suggest a potential treatment effects of imatinib 
on circulating CD133 mRNA levels. Nonetheless, larger prospective study with serial CD133 mRNA levels performed at diagnosis, pre- and posttreatment and at time of progression along with circulating tumor cells enumerations are needed to assess the value of CD133 mRNA as a surrogate marker. Discussion To our knowledge, this is the first report to demonstrate that peripheral blood mononuclear CD133 mRNA level correlate with the response to imatinib in patients with GIST. Plasma VEGF levels also appear to correlate with reduction in the tumor volume secondary to drug treatment, however, we found no correlation between peripheral blood mononuclear CD133 mRNA levels and plasma VEGF levels. CD133 mRNA when coupled with epithelial markers was able to predict colon cancer relapse and survival The current study highlights the importance of CD133 mRNA as peripheral blood biomarkers for predicting imatinib sensitivity and monitoring the disease progress in the surveillance setting in GIST. Gastrointestinal stromal tumors have activating KIT or PDGFRA gene mutations. Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. CD133 is a member of prominin family but its functions remains unknown and was found in almost all tissues including retina. Neither tissue nor tumor specific, CD133 identifies with stem/progenitor cells, as well as a host of CSC from variety of tumors notably GBM, 23964788 colon, lung,and prostate etc. Although, CD133 protein expression was found to be universal expressed in GIST, it might not CD133 Correlates with Response to Treatment Lack of correlation of the progression free survival and CD133 mRNA levels may be compounded by a number of factors including lack of clear imaging parameters in 2003 as CHOI criteria was later introduced to address frequent discrepancies of CT scan imaging in interpreting tumor response and progression in patients with GIST tumors treated with imatinib. Again, the sample size is still too small to address these questions definitively. In summary, peripheral blood mononuclear CD133 mRNA levels represent a potential surrogate for predicting response to imatinib in GIST patients and it is useful in monitoring the disease course during following up. Peripheral bloo
