Oliceridine versus sufentanil: a systematic review and meta-analysis of postoperative nausea and vomiting.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, with over 900,000 new cases diagnosed annually []. Despite significant improvements in survival for some patients through surgical resection, liver transplantation, and targeted therapies, the 5-year survival rate for HCC remains at only 18%, primarily due to the high propensity of the disease to metastasize and associated chemoresistance [, ]. Consequently, a critical and urgent need exists to elucidate the key drivers of HCC progression and to develop clinically valuable prognostic biomarkers and therapeutic targets. Recent studies have highlighted the critical role of neurotransmitters in tumor progression. Within the tumor microenvironment (TME), various cell types—including tumor cells, immune cells, and other stromal cells—can secrete neurotransmitters that modulate key tumor biological processes such as tumorigenesis, metastasis, and immune evasion. Moreover, signaling between neurotransmitters and their receptors is pivotal to tumor initiation and progression, representing a burgeoning area of oncological research [–]. For instance, norepinephrine-mediated activation of β-adrenergic receptors (β-AR) has been shown to suppress the effector functions of CD8 T cells, thereby compromising the efficacy of immune checkpoint inhibitors []; In murine colorectal carcinoma models, elevated acetylcholine levels correlated with increased tumor proliferation and metastasis; these effects were effectively abrogated by M3 muscarinic receptor antagonists []; Similarly, γ-aminobutyric acid (GABA) was demonstrated to promote tumor angiogenesis and progression in lung adenocarcinoma by upregulating FGF2 expression in macrophages via GABA-A receptor signaling []. Collectively, these findings establish neurotransmitter receptors as central regulators of tumor biology and highlight their potential as novel therapeutic targets for improving HCC prognosis. The GABA receptor family comprises two major classes: ligand-gated ion channels (GABA and GABA) and G protein-coupled receptors (GABA). GABA receptors function as heteropentameric chloride channels that mediate rapid synaptic inhibition []. Among the subunits of these receptors, the delta subunit (GABRD) exhibits distinctive tissue distribution and pharmacological properties. Predominantly localized to extrasynaptic regions, GABRD assembles with α6 or α4 subunits to form high-affinity receptor complexes that generate tonic inhibition, thereby fine-tuning cellular excitability [, ]. While dysregulation of GABRD is strongly associated with neuropsychiatric disorders such as depression and epilepsy [, ], emerging evidence also points to its significant involvement in oncogenesis across various cancer types. GABRD knockdown was shown to inhibit the proliferation of prostate cancer cells []; In esophageal squamous cell carcinoma, GABRD forms a complex with DEPDC1B to activate the PI3K/Akt/mTOR pathway, driving tumor progression []; In gastric cancer, GABRD accelerates tumor growth through modulation of CCND1 signaling []; GABRD also promotes breast cancer metastasis by activating Ca -dependent PKC-CREB signaling [], and meanwhile is associated with poor clinical outcomes in colorectal cancer [–]. Whereas, the molecular mechanisms by which GABRD regulates HCC tumorigenesis remain entirely unexplored.