Purpose: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC).Experimental Design: In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).Results: Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n ¼ 220) and a validation cohort (n ¼ 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation.Conclusions: SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.
As a family of chromatin remodeling proteins, metastasis-associated proteins (MTAs) have shown to be the master regulators in both physiological and pathological contexts. Although MTA3 is the latest being identified in MTA family, it has started to draw as much attention as the other family members. MTA3 is expressed in various tissues and is associated with different physiological functions. In cancerous context, both MTA1 and MTA2 are generally considered as oncogenes because they are capable of enhancing metastasis. However, MTA3 appears to play more complicated roles in cancers depending on the contexts. As a tumor suppressor, MTA3 usually down-regulates Snail, the master regulator of epithelium-mesenchymal transition, and subsequently represses cancer cell invasion and migration. Additionally, MTA3 may function by enhancing cancer cell differentiation without affecting proliferation in certain cancers. On the other hand, MTA3 might function in oncogene - related properties similarly as MTA1 and MTA2. In this review, we summarize our current understanding about MTA3 in normal development, cancers as well as other human diseases by comparing the similarities and differences between MTA3 and the other members of the MTA family.
<p>Raw data 2-Supplementary Zip including supplementary tables with the qRT-PCR data from the patient cohorts with the amplification profile data (training cohort)</p>
<p>Raw data 3-Supplementary Zip including supplementary tables with the qRT-PCR data from the patient cohorts with the amplification profile data (validation cohort)</p>
<p>Raw data 1-Supplementary Zip including supplementary tables with the qRT-PCR data from the patient cohorts with the amplification profile data (tissue archive and discovery cohort)</p>
<p>Raw data 3-Supplementary Zip including supplementary tables with the qRT-PCR data from the patient cohorts with the amplification profile data (validation cohort)</p>
<div>AbstractPurpose:<p>Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal <i>GOLM1-NAA35</i> chimeric RNA (se<i>G-N</i>chiRNA) in esophageal squamous cell carcinoma (ESCC).</p>Experimental Design:<p>In a retrospective study, the prognostic significance of <i>G-N</i>chiRNA was determined in ESCC tissues. The correlation between se<i>G-N</i>chiRNA and circulating exosomal or tumoral <i>G-N</i>chiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, se<i>G-N</i>chiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).</p>Results:<p>Exosomal <i>G-N</i>chiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. Se<i>G-N</i>chiRNA levels reflected tumor burden <i>in vivo</i> and correlated with tumor <i>G-N</i>chiRNA levels. In prospective studies of a training cohort (<i>n</i> = 220) and a validation cohort (<i>n</i> = 102), se<i>G-N</i>chiRNA levels were substantially reduced after ESCC resection. Moreover, se<i>G-N</i>chiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in se<i>G-N</i>chiRNA levels also predicted PFS of patients after chemoradiation.</p>Conclusions:<p>Se<i>G-N</i>chiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.</p></div>
<div>AbstractPurpose:<p>Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal <i>GOLM1-NAA35</i> chimeric RNA (se<i>G-N</i>chiRNA) in esophageal squamous cell carcinoma (ESCC).</p>Experimental Design:<p>In a retrospective study, the prognostic significance of <i>G-N</i>chiRNA was determined in ESCC tissues. The correlation between se<i>G-N</i>chiRNA and circulating exosomal or tumoral <i>G-N</i>chiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, se<i>G-N</i>chiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).</p>Results:<p>Exosomal <i>G-N</i>chiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. Se<i>G-N</i>chiRNA levels reflected tumor burden <i>in vivo</i> and correlated with tumor <i>G-N</i>chiRNA levels. In prospective studies of a training cohort (<i>n</i> = 220) and a validation cohort (<i>n</i> = 102), se<i>G-N</i>chiRNA levels were substantially reduced after ESCC resection. Moreover, se<i>G-N</i>chiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in se<i>G-N</i>chiRNA levels also predicted PFS of patients after chemoradiation.</p>Conclusions:<p>Se<i>G-N</i>chiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.</p></div>
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