Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma

Abstract

Background. Hepatectomy remains one of the most effective treatments for patients with hepatocellular carcinoma (HCC); however, it can lead to serious complications. Irisin, a key regulator of energy metabolism, is secreted into the circulation by shedding of the extracellular portion of the fibronectin type III domain-containing 5 (FNDC5). We have shown that irisin administration alleviates liver ischemia-reperfusion injury in mice. However, the role of preoperative irisin levels in HCC patients who underwent hepatectomy remained unknown. The purpose of this study was to determine how irisin expression changes in HCC and to explore the relationship between preoperative serum irisin levels and complications after hepatectomy. Methods. FNDC5/irisin expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. A total of 219 participants, including 102 healthy controls and 117 HCC patients, were recruited in this study. All HCC patients underwent hepatectomy at the First Affiliated Hospital of the Xi’an Jiaotong University. Preoperative serum irisin levels were measured by ELISA. Postoperative complications were assessed using the comprehensive complication index (CCI) score. The Pearson rank correlation coefficient was computed to assess the correlation between preoperative serum irisin levels and postoperative CCI scores. Results. In TCGA dataset, FNDC5/irisin expression was downregulated in HCC tissues (P<0.001). Similarly, serum irisin levels were decreased in HCC patients (P<0.001). Low preoperative serum irisin levels were significantly correlated with high CCI scores after hepatectomy. Conclusions. Irisin may be a novel serum biomarker in the diagnosis of HCC and a predictor of complications after hepatectomy.

Current Evidence of the Role of the Myokine Irisin in Cancer

“…Zhang et al measured the serum irisin levels in healthy subjects and in patients with HCC before and after hepatectomy. The serum irisin levels were significantly reduced in the cancer patients [ 94 ]. Low serum irisin levels before hepatectomy were significantly correlated with high postoperative complications (high comprehensive complication index (CCI) scores) [ 94 ].…”

“…The serum irisin levels were significantly reduced in the cancer patients [ 94 ]. Low serum irisin levels before hepatectomy were significantly correlated with high postoperative complications (high comprehensive complication index (CCI) scores) [ 94 ]. The authors suggested a potential of irisin to be used as a serum biomarker in the diagnosis of HCC and a predictor of the complications after hepatectomy.…”

“…Zhang et al found that the expression of FNDC5/irisin in the tumor tissue of HCC patients was reduced [ 94 ] compared to the tissue from control healthy subjects.…”

“…Overall, the evidence from the in vivo studies does not provide a clear picture of the exact role of irisin in cancer. The majority of the studies showed lower serum irisin levels in breast [ 91 , 92 ], hepatocellular carcinoma [ 94 , 95 ], colorectal [ 96 ], bladder [ 98 ] and prostate [ 99 ] cancer patients compared to healthy humans. Three studies found higher serum irisin levels in hepatocellular carcinoma [ 93 ], renal [ 97 ] and bladder [ 100 ] cancer patients compared to healthy humans ( Table 3 ).…”

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

“…It is well known that KIF20A is abnormally highly expressed in many tumors and is associated with a poor prognosis, including for PCa [ 16 , 17 , 19 ]. The association between FOXM1 and KIF20A in PCa was therefore investigated, with the protein levels of FOXM1 and KIF20A in DU145, VCaP, and their resistant cells being assessed.…”