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Identification and Validation of Differentially Expressed mRNAs From Peripheral Leukocytes for Acute Stanford Type A
Yueyun Zhou1, Changying Chen2, Jian Li1
1Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu China.
Background:
Acute Stanford type A aortic dissection (ATAAD) is lethal and has a high mortality rate, but few useful biomarkers are available for its diagnosis. This study aimed to identify and validate differentially expressed mRNAs in ATAAD from peripheral leukocytes.
Methods:
RNA sequencing was performed using peripheral blood leukocyte samples from 8 patients with ATAAD and 20 controls to screen differentially expressed mRNAs. A 2-stage case-control study consisting of 178 patients with ATAAD and 178 healthy controls was conducted to validate the 20 upregulated and 20 downregulated differentially expressed mRNAs. Then, a stage 3 case-control study consisting of 64 patients with ATAAD, 64 patients with acute myocardial infarction, and 64 controls was used for discriminative evaluation. Receiver operating characteristic curves were used to assess the diagnostic value of the differentially expressed mRNAs.
Results:
A total of 35 mRNAs were successfully detected in stage 1, and 32 mRNAs presented differential expression (P<0.05). Twenty-four mRNAs were further validated in stage 2 (P<0.05). Nineteen mRNAs were verified to be differentially expressed from acute myocardial infarction in stage 3 (P<0.05). OLAH, MCEMP1, HP, ADAMTS2, and SIGLEC8 had the 5 highest area under the curve values for diagnosing ATAAD, which were 0.941, 0.927, 0.908, 0.888, and 0.883, respectively. The combined areas under the curve of the 5 mRNAs was 0.965 for diagnosing ATAAD and 0.918 for discriminating ATAAD from acute myocardial infarction.
Conclusions:
OLAH, MCEMP1, HP, ADAMTS2, and SIGLEC8 have potential to be biomarkers for ATAAD, which provide a promising approach for predicting ATAAD and distinguishing it from acute myocardial infarction.
