GSE123605
Predicting Postoperative Liver Dysfunction Based on Blood Derived MicroRNA Signatures
Treatment options and reliable predictive marker to determine patients at risk to develop postoperative LD and to define the optimal time point of liver resection are limited. Accordingly, there is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery, specifically as current markers are often expensive, time consuming and sometimes invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic and treatment response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative LD after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature - consisting of miRNAs 151a-5p, 192-5p and 122-5p - that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stay and even mortality prior to surgery with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Given the clinical relevance of predicting potentially fatal postoperative clinical outcome after liver resection, our data demonstrate the clinical utility of a novel miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in tailoring the optimal time point of surgery to each individual patient. Thereby, our data might help to tailor surgical strategies to the specific risk profile of individual patients. Overall design: Examination of 48 baseline plasma samples by Illumina NextSeq 500 sequencing taken prior to partial hepatectomy. 21 samples from patients with post-operative liver dysfunction. 27 samples from patients without post-operative liver dysfunction. Please note that there are two patients who received hepatic surgery because of liver cirrhosis, but did not suffer from a cancerous disease (characteristics: cancer type = none). The main outcome of this study was post-operative liver dysfunction (characteristics: Liver Dysfunction) and the type of cancer was provided as supporting information to give background about the reason why patients required liver surgery. Mostly, lesions due to three types of cancer were the reason for surgery, and, in only two cases, cirrhosis.