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Liver Stromal Cells Restrict Macrophage Maturation and Stromal IL-6 Limits the Differentiation of Cirrhosis-linked Macrophages

ABSTRACT: Liver disease is the cause of approximately two million deaths globally per year, yet effective therapies are lacking. Iterative tissue injury leads to prolonged inflammation, extensive fibrosis, and the possible progression to deadly chronic-end stage disease, such as cirrhosis and hepatocellular carcinoma (HCC). In this study we investigated the ability of liver stromal cells to effect macrophage maturation and differentiation by using an in vitro human stromal-myeloid coculture systems and single cell RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168933 | GEO | 2022/01/31

REPOSITORIES: GEO

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Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens

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Liver Stromal Cells Restrict Macrophage Maturation and Stromal IL-6 Limits the Differentiation of Cirrhosis-linked Macrophages

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