Mendelian randomization explores the causal relationships between obesity, diabetes, inflammation and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Observational studies have revealed various risk factors associated with NAFLD, while the causal relationships between NAFLD and clinical diseases (including obesity, diabetes and inflammation) remain unclear. In this study, based on the genome-wide association study (GWAS) data, a two-sample Mendelian randomization (MR) analysis was conducted to evaluate the causality between NAFLD and 6 clinical indicators, including body mass index (BMI), waist-to-hip ratio (WHR), C-reactive protein (CRP), fasting blood glucose (FG), fasting insulin (FI), and glycosylated hemoglobin (HbA1c). MR is based on Mendel's law of inheritance, which uses genetic variation as a toll variable to affect the health of a population to infer causal effects in the presence of unobserved confounding. Inverse variance weighted method was the main MR method. In addition, we performed multiple steps of variable screening in the method to ensure that we were conducting the study under the MR assumption. In the MR analysis, a higher WHR (P = .0078; OR = 1.008; 95% CI, 1.002-1.013) was genetically predicted to be causally associated with an increased risk of NAFLD, while patients with higher HbA1c had a lower risk of NAFLD (P = .0437; OR = 0.44; 95% CI, 0.20-0.97). Our results showed that the genetically driven WHR and HbA1c might be potential causal factors for NAFLD, while BMI, FG, FI, and CRP were not causal factors for NAFLD, which explained the promoting role of WHR and HbA1c in the occurrence and development of NAFLD. Our finding hence revealed new insights into how nature and nurture factors underpin NAFLD, providing positive effect on the causes and prevention of this disease.

[Retracted] KIFC1 promotes the proliferation of hepatocellular carcinoma in vitro and in vivo.

[This retracts the article DOI: 10.3892/ol.2019.10985.].

Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection.

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as neutrophil × monocyte/lymphocyte count (109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC (P < 0.040). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC (P < 0.015). In addition, in small-duct type ICC, NLR and LMR were correlated with OS (P < 0.025), whilst CEA and CA242 were correlated with DFS (P ≤ 0.010). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.

KIFC1 promotes the proliferation of hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a common type of malignant tumor worldwide with a high mortality rate. In the past 20 years, the morbidity rate of HCC has increased. Progress has been made in the clinical diagnosis and therapy for HCC. However, due to the high heterogeneity and metastasis targeted therapy for HCC exhibits great promise, and novel therapeutic targets for HCC are urgently required. Kinesin family member C1 (KIFC1) is a member of the kinesin superfamily of proteins. Previous studies have indicated a potential association between KIFC1 and cancer progression. However, the potential role of KIFC1 in the development of HCC remains unclear. The present study aimed to explore the function of KIFC1 in HCC. Immunohistochemical (IHC) assays were performed to explore the KIF15 expression levels in 74 samples of HCC and corresponding non-tumor tissues. The potential association between KIF15 expression levels and clinical features was analyzed, and the effects of KIF15 on cell proliferation of HCC were detected by colony formation and MTT assays. In addition, the proliferation-related proteins Ki67 and PCNA were detected by western blotting. The possible effects of KIF15 on tumor growth were measured in mice. The results demonstrated that a high expression level of KIFC1 was associated with poor prognosis of HCC. Further results indicated that KIFC1 promoted cell proliferation of HCC in vitro. In addition, knockdown of KIFC1 suppressed tumor formation and growth in mice. Therefore, these results provide a potential therapeutic target for the treatment of HCC.