The association of leptin and adiponectin with hepatocellular carcinoma risk and prognosis: a combination of traditional, survival, and dose-response meta-analysis

Abstract

Background An increasing number of studies have focused on the association between leptin, adiponectin levels and the risk as well as the prognosis of hepatocellular carcinoma. However, the reported results are conflicting. Methods A meta-analysis was performed to assess the correlation between leptin, adiponectin levels and risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library and EMBASE databases were searched, including references of qualifying articles. Titles, abstracts, and main texts were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data. Results Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group had significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000), the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group had significantly higher adiponectin levels than the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (− 0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = − 0.51, 95% CI (− 1.30, 0.29), P = 0.213). The leptin rs7799039 polymorphism was associated with increased risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766). Conclusion The study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis

“…Some studies reported that adiponectin might confer a protective effect on the development and progression of GICs due to its features of anti‐inflammation and anti‐proliferation 5,29–32 . On the other hand, there were evidences from population‐based studies suggested no correlation between adiponectin and the risk of GICs 9,33,34 and that adiponectin conferred an increased risk for liver cancer 35,36 . The inconsistent findings of the observational studies indicated a putative role of adiponectin in the carcinogenesis of GICs and greatly justified the necessity of our MR study.…”

Obesity and cholangiocarcinoma: A review of epidemiological and molecular associations

“…Contrariwise, adiponectin levels have been shown as both a positive and negative predictor of cancers. 64,65 These findings likely highlight the importance of adiponectin signaling, known to be altered in obesity. 66 Considering that the study of adiponectin in CCA is more limited than that of leptin, additional evidence from further in vitro and in vivo studies is necessary to understand this pathway better.…”

Role of Leptin in Non-Alcoholic Fatty Liver Disease

“…However, the procarcinogenic role of leptin in HCC patients seems clear. Additionally, high leptin levels alone are also considered to increase the risk of HCC [93]. In fact, in vitro studies suggest that this hormone is increased during the proliferation, migration, and invasiveness of HCC cells through activation of PI3K/AKT signaling pathways, mainly in obese patients [44] and have been demonstrated to take part in the angiogenesis process [94], as well as both JAK2/STAT and ERK pathways [95].…”