Longitudinal studies can identify distinct inflammatory cytokines associated with the inhibition or progression of liver cancer

Abstract

Abbreviations: CD, chow diet; DIAMOND, diet-induced animal model of nonalcoholic fatty liver disease; HCC, hepatocellular carcinoma; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; WD, Western diet. AbstractBackground and Aims: Chronic diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are associated with chronic inflammation. However, controversial reports as to the key cytokines involved in the process of chronic inflammation hinder development of targeted therapies for patients. This is because, chronic inflammatory process cannot be fully understood by studying the mechanisms of the disease in a short-term or isolated fashion. Understanding of the trend of inflammatory cytokines through longitudinal studies could provide a profound insight into the process of disease progression. Methods:We performed a longitudinal analysis of inflammatory cytokines/ chemokines and faecal microbiome dysbiosis associated with the diet-induced progression of NAFLD to HCC in diet-induced animal model of NAFLD comparing males and females, since males show a higher incidence of these diseases than females do. Results:Longitudinal analyses revealed that a transient and timely increase in LIF and TMIP1 was associated with the inhibition of the progression of NAFLD to HCC in females. On the other hand, chronically increasing trends in CCL12, CCL17, CXCL9 and LIX/CXCL5 were associated with the promotion of the progression of NAFLD to HCC in males. Conclusions:We provided empirical evidence that a methodological shift from snapshot observations to longitudinal data collection and analysis can provide a better understanding of chronic liver diseases. K E Y W O R D S chronic inflammation, HCC, longitudinal research, NAFLD, NASH | 469 MIRSHAHI et Al.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease

“…cxcl11 . 6 is homologous to human cxcl9 , which was shown to be upregulated in patients with NAFLD and associated with the promotion of the progression of NAFLD to hepatocellular carcinoma ( 109, 110 ). It is tempting to speculate that cxcl11 .…”

“…cxcl11.6/dpp4 showed specifically high activity between inflammatory macrophages and hepatocytes. cxcl11.6 is homologous to human cxcl9, which was shown to be upregulated in patients with NAFLD and associated with the promotion of the progression of NAFLD to hepatocellular carcinoma (109,110). It is tempting to speculate that cxcl11.6 may be considered a candidate gene for studying the inflammatory response of inflammatory macrophages and hepatocytes in the context of NAFLD in a zebrafish model.…”

CXCL5 Has Potential to Be a Marker for Hepatocellular Carcinoma Prognosis and Was Correlating With Immune Infiltrates

“…The expression level of CXCR2 in HCC was significantly higher than normal liver tissues, and the expression levels of CXCR2 mRNA and protein were associated with intrahepatic metastasis, portal vein tumor thrombus, and poor differentiation ( 26 ). A longitudinal study has indicated that the chronically increasing trend of CXCL5 were associated with the promotion of the progression of NAFLD to HCC in males ( 27 ). Xu’s study had shown that overexpression of CXCL5 in HCC cells has higher metastatic potential, which also demonstrated that CXCL5/CXCR2 and ERK1/2 highway may play an important role in the migration of HCC ( 28 ).…”

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

“…To date, no further reports have been made on the role of mCCL12 in liver disease, with the exception of a longitudinal analysis that found that male mice, a chronically increasing trend in mCCL12 was associated with the progression of NAFLD to HCC (30). However, based on the high homology of mCCL12 with the human CCL2 protein (68%), mCCL12 may also play an essential role in liver pathology, which needs to be confirmed by further studies.…”