Abstract
BackgroundIn recent years, the relationship between tumor-associated macrophages (TAMs) and solid tumors has become a research hotspot. This study aims to explore the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma (HCC) to provide new methods of treatment for HCC.MethodsThe study selected 343 HCC patients with complete survival information (survival time > = 1 month) in the Cancer Genome Atlas (TCGA) as study subjects. Kaplan-Meier survival analysis assisted in determining the relationship between macrophage infiltration and overall survival (OS), and Pearson correlation tests were used to identify metabolic reprogramming genes (MRGs) associated with tumor macrophage abundance. Lasso regression algorithms were used on prognosis-related MRGs identified by Kaplan-Meier survival analysis and univariate Cox regression analysis to construct a risk score; another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) was used to verify prognostic signature externally.ResultsA risk score composed of 8 metabolic genes could accurately predict the OS of a training cohort (TCGA) and a testing cohort (ICGC). The risk score could be widely used for people with different clinical characteristics, and it is a predictor that is independent of other clinical factors that affect prognosis. As expected, compared with the low-risk group, the high-risk group exhibited an obviously higher macrophage abundance, together with a positive correlation between the risk score and the expression levels of three commonly used immune checkpoints (PD1, PDL1, and CTLA4).ConclusionOur study constructed and validated a novel eight-gene signature for predicting HCC patient OS, which may contribute to clinical treatment decisions.
Highlights
In recent years, the relationship between tumor-associated macrophages (TAMs) and solid tumors has become a research hotspot
Identification and annotation of TAM-related metabolic genes (TRMGs) We observed that patients with a higher abundance of macrophage infiltration had a poorer prognosis (Fig. 2a), which prompted us to identify prognostic biomarkers of hepatocellular carcinoma (HCC) according to the degree of macrophage infiltration
We identified 1382 metabolic genes with different expression levels between high macrophage infiltration and low macrophage infiltration patients (Fig. 2b), and 192 genes were significantly correlated with macrophage infiltration (Fig. 2c)
Summary
The relationship between tumor-associated macrophages (TAMs) and solid tumors has become a research hotspot. To adapt to the decreased nutrients and oxygen available in the tumor microenvironment (TME) and to maintain the rapid proliferation and material synthesis of tumor cells, a series of changes to the metabolic processes of tumor cells occur that lead to the increase in related metabolites, such as lactate, nitrous oxide, reactive oxygen species, prostaglandin, and arachidonic acid, in the tumor microenvironment, creating an inflammatory microenvironment [10, 11] These changes affect the function of tumor associated macrophages (TAMs), including changes in cytokines and angiogenic factors, which may prompt tumor progression and metastasis [12]
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