Journal
MOLECULAR CANCER
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12943-022-01684-9
Keywords
Exosome; Multi-omics characteristics of RNAs; Advanced gastric cancer; Neoadjuvant chemotherapy; Biomarker panel for efficacy prediction
Categories
Funding
- National Natural Science Foundation of China [U20A20371, 81872502, 81972758, 31870805]
- Natural Science Foundation of Beijing [7222023]
- National High Technology Research and Development Program of China [2014AA020603]
- Beijing Municipal Medical Research Institutes (Beijing Medical Research Institute) [2019-1]
- Double First Class disciplinary development Foundation of Peking University [BMU2019LCKXJ011]
- Beijing municipal administration of hospitals' youth program [QML20181102, QML20201104]
- Chinese Society of Clinical Oncology (CSCO) Research Foundation [Y-HR2019-0375]
- Beijing Municipal Administration of Hospitals Incubating Program [PX2019040]
- Research Fund for Young Scholars of Beijing [2018000021469G265]
- Clinical Medicine Plus X-Young Scholars Project, Peking University
- Fundamental Research Funds for the Central Universities [PKU2020LCXQ001]
- Science Foundation of Peking University Cancer Hospital [2020-6, 2022-3]
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This study aimed to develop a non-invasive blood test using an exosome-derived RNA model to predict the efficacy of neoadjuvant chemotherapy in gastric cancer patients. Through RNA sequencing, a variety of miRNAs, mRNAs, and lncRNAs associated with treatment response were identified and validated in an independent cohort. Furthermore, a panel of 6 exosome-derived RNAs was established to accurately distinguish responders from non-responders to fluorouracil-based neoadjuvant chemotherapy.
At present, there is no validated marker to identify the subpopulation of patients with advanced gastric cancer (AGC) who might benefit from neoadjuvant chemotherapy (NACT). In view of this clinical challenge, the identification of non-invasive biomarkers for efficacy prediction of NACT in patients with AGC is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy-based assay by using an exosome-derived RNAs model based on multi-omics characteristics of RNAs. We firstly used a multi-omics strategy to characterize the mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) profiles of circulating exosome enriched fractions in responders to NACT paired with non-responders, using RNA sequencing. Finally, numerous miRNAs, mRNAs and lncRNAs were identified to be associated with the response to NACT in patients with AGC, and it was validated in an independent cohort with promising AUC values. Furthermore, we established a 6-exosome-RNA panel that could robustly identified responders from non-responders treated with fluorouracil-based neoadjuvant chemotherapy.
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