Multifaceted role of FAM210B in hepatocellular carcinoma: Implications for tumour progression, microenvironment modulation and therapeutic selection

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 16; pp. e70031 - n/a
• Main Authors: Pan, Xianzhu, Xu, Jun, Zhou, Yuanqin
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc
• Subjects: Biomarkers; Cell growth; Cell migration; Cell proliferation; CTLA-4 protein; Cytosol; drug sensitivity; Epigenetics; FAM210B; Genomic instability; Hepatocellular carcinoma; Immune checkpoint; Immune response; Immunohistochemistry; Immunotherapy; Liver cancer; Liver diseases; Localization; Medical prognosis; Metabolic pathways; Microenvironments; Original; Tumors; tumour microenvironment
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70031

Hepatocellular carcinoma (HCC) is a common and lethal liver cancer characterized by complex aetiology and limited treatment options. FAM210B, implicated in various cancers, is noteworthy for its potential role in the progression and treatment response of HCC. Yet, its expression patterns, functional impacts and correlations with patient outcomes and resistance to therapy are not well understood. We employed a comprehensive methodology to explore the role of FAM210B in HCC, analysing its expression across cancers, subcellular localization and impacts on cell proliferation, invasion, migration, biological enrichment and the immune microenvironment. Additionally, we investigated its expression in single cells, drug sensitivity and relationships with genomic instability, immunotherapy efficacy and key immune checkpoints. While FAM210B expression varied across cancers, there was no notable difference between HCC and normal tissues. Elevated levels of FAM210B were associated with improved survival outcomes. Subcellular analysis located FAM210B in the plasma membrane and cytosol. FAM210B was generally downregulated in HCC, and its suppression significantly enhanced cell proliferation, invasion and migration. Biological enrichment analysis linked FAM210B to metabolic and immune response pathways. Moreover, its expression modified the immune microenvironment of HCC, affecting drug responsiveness and immunotherapy outcomes. High expression levels of FAM202B correlated with increased resistance to sunitinib and enhanced responsiveness to immunotherapy, as evidenced by associations with tumour mutation burden, PDCD1, CTLA4 and TIDE scores. FAM210B exerts a complex influence on HCC, affecting tumour cell behaviour, metabolic pathways, the immune microenvironment and responses to therapy.