Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

BACKGROUND & AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication. METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray. Area under the receiver operator characteristic curve (AUROC) and least absolute shrinkage and selector operation regression analyses were used to prioritize miRNAs that discriminated patients with ESCC from controls. Using quantitative reverse transcription polymerase chain reaction, the candidates were measured in a discovery cohort (n = 72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n = 342) and validated in an internal cohort (n = 207) and an external cohort (n = 226). RESULTS: The microarray analysis identified 7 miRNAs for distinguishing patients with ESCC from control subjects. Because 1 was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified patients with all-stage ESCC in the training cohort (AUROC = 0.968) and was successfully validated in 2 independent cohorts. Importantly, this signature could distinguish patients with early-stage (stage Ⅰ/Ⅱ) ESCC from control subjects in the training cohort (AUROC = 0.969, sensitivity = 92.00%, specificity = 89.17%) and internal (sensitivity = 90.32%, specificity = 91.04%) and external (sensitivity = 91.07%, specificity = 88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival. CONCLUSIONS: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA

MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA