Gene trail of polarized M2 macrophage decodes tumor heterogeneity and recommendation for therapy of hepatocellular carcinoma

Abstract M2 macrophages are known to substantially influent tumor invasion and metastasis, leading to diverse clinical outcomes. This study aimed to identify a novel biomarker associated with M2 macrophages and assess its prognostic significance in hepatocellular carcinoma. Genes exhibiting a significant correlation with M2 cells were identified using single-cell RNA sequencing (scRNA-Seq) and WGCNA analysis. Subsequently, patients were stratified into two distinct groups using the consistency clustering method. Following this categorization, an in-depth investigation was conducted to explore the prognostic implications, biological attributes, genomic variations, and the immune landscape within each cluster. Moreover, the potential efficacy of drug treatment and the anticipated impact of immunotherapy were also assessed.Based on the analysis of M2 cell development trace genes and the findings from WGCNA, a total of 17 target genes were identified, leading to the identification of two distinct clusters with varying clinical outcomes. Group C1 was characterized as cell proliferative liver cancer, whereas Group C2 was classified as lipid metabolic liver cancer. Furthermore, two anticancer drugs were analyzed. Patients in group C1 exhibited a higher sensitivity to erlotinib, whereas patients in group C2 demonstrated a greater sensitivity to rapamycin. Moreover, immunotherapy appeared to be more suitable for patients in group C1. This study significantly enhances the existing understanding of the involvement of M2 cells in the biological and prognostic prediction of hepatocellular carcinoma, thereby offering potential benefits in terms of enhancing clinical management and ultimately improving clinical outcomes.