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- Title
Histamine-related genes participate in the establishment of an immunosuppressive microenvironment and impact the immunotherapy response in hepatocellular carcinoma.
- Authors
Zhang, Xianzhou; Zheng, Peng; Meng, Bo; Zhuang, Hao; Lu, Bing; Yao, Jun; Han, Feng; Luo, Suxia
- Abstract
Chronic inflammation is pivotal in the pathogenesis of hepatocellular carcinoma (HCC). Histamine is a biologically active substance that amplifies the inflammatory and immune response and serves as a neurotransmitter. However, knowledge of histamine's role in HCC and its effects on immunotherapy remains lacking. We focused on histamine-related genes to investigate their potential role in HCC. The RNA-seq data and clinical information regarding HCC were obtained from The Cancer Genome Atlas (TCGA). After identifying the differentially expressed genes, we constructed a signature using the univariate Cox proportional hazard regression and least absolute shrinkage and selection operator (LASSO) analyses. The signature's predictive performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Furthermore, drug sensitivity, immunotherapy effects, and enrichment analyses were conducted. Histamine-related gene expression in HCC was confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). A histamine-related gene prognostic signature (HRGPS) was developed in TCGA. Time-dependent ROC and Kaplan–Meier survival analyses demonstrated the signature's strong predictive power. Importantly, patients in high-risk groups exhibited a higher frequency of TP53 mutations, elevated immune checkpoint-related gene expression, and increased infiltration of immunosuppressive cells—indicating a potentially favorable response to immunotherapy. In addition, drug sensitivity analysis revealed that the signature could effectively predict chemotherapy efficacy and sensitivity. qRT-PCR results validated histamine-related gene overexpression in HCC. Our findings demonstrate that inhibiting histamine-related genes and signaling pathways can impact the therapeutic effect of anti-PD-1/PD-L1. The precise predictive ability of our signature in determining the response to different therapeutic options highlights its potential clinical significance.
- Subjects
RECEIVER operating characteristic curves; GENETIC overexpression; GENE expression; GENES; POLYMERASE chain reaction; HEPATOCELLULAR carcinoma
- Publication
Clinical & Experimental Medicine, 2024, Vol 24, Issue 1, p1
- ISSN
1591-8890
- Publication type
Article
- DOI
10.1007/s10238-024-01399-9