A RASSF8‐AS1 based exosomal lncRNAs panel used for diagnostic and prognostic biomarkers for esophageal squamous cell carcinoma. Issue 23 (20th October 2022) - Xie, Kai
Abstract: Background: Exosomal long non‐coding RNA (lncRNA) has been shown to be potential biomarker for cancer diagnosis and follow up. However, little is known about its application in esophageal squamous cell carcinoma (ESCC) detection. Here, we sought to develop a novel diagnostic model based on serum exosomal lncRNAs to improve ESCC screening efficiency. Methods: A multiphase, case‐control study was conducted among 140 ESCC patients and 140 healthy controls. Microarray screening was performed to acquire differentially expressed exosomal lncRNAs in the discovery phase. The diagnostic model Index I was constructed based on a panel of three lncRNAs using logistic regression in the training phase, and were confirmed in a subsequent validation phase. A receiver operating characteristic (ROC) curve was generated to calculate the diagnostic value. The effects of the selected lncRNAs level on ESCC mortality were evaluated using a Cox hazard regression model and Kaplan‐Meier curve analysis, and the expression level with clinicopathological features was also calculated. Finally, we explored the oncogenic potential of candidate lncRNA RASSF8‐AS1 in vitro and by target mRNA sequencing. Results: Index I was able to discriminate ESCC patients from healthy controls, and showed superiority to classic tumor biomarkers. Moreover, serum levels of the exosomal lncRNAs correlated with clinicopathological features and prognosis. The in vitro assays showed that RASSF8‐AS1 played an oncogenic role in ESCC. Target mRNA scanning results suggested involvement of RASSF8‐AS1 in tumor immunity and metabolism. Conclusion: The newly identified serum exosomal lncRNAs could be used as new biomarkers for ESCC, and showed oncogenic potential in ESCC. Abstract : A multiphase, case–control study was conducted among 140 ESCC patients and 140 healthy controls (a). Microarray screening was performed to acquire differentially expressed exosomal lncRNAs in the discovery phase. Joint microarray results from serum and tissue samples determined the candidate lncRNAs (b). A diagnostic model Index I was constructed based on a panel of three lncRNAs, and compared with the traditional‐ biomarker based model Index II in training and validation phases separately (c and d). Kaplan–Meier analysis indicated that Index I level correlated with ESCC patient survival, also suggesting a predictive role for ESCC prognosis (e).