Pan-cancer analysis identifies FAM49B as an immune-related prognostic maker for hepatocellular carcinoma

Abstract

Family with sequence similarity 49, member B (FAM49B) is highly expressed in many tumors, its role in malignant tumors especially in hepatocellular carcinoma (HCC) remains uncertain. We first evaluated the expression, clinical features, and prognostic value of FAM49B using RNA-seq and clinical data from The Cancer Genome Atlas. We further assessed the role of FAM49B in the tumor immune microenvironment. The correlation of FAM49B with the sensitivity of 192 anti-cancer drugs was analyzed using data from Genomics of Drug Sensitivity in Cancer database. qRT-PCR assay was used to validate the expression of FAM49B in HCC. FAM49B was expressed at high levels in most tumor types, including HCC. High FAM49B expression predicted poor survival in patients with HCC. We also found that FAM49B expression was negatively associated with the infiltration levels of immune killer cells, including NK cells, and positively associated with immunosuppressive cells, including Tregs and Central Memory T cell (Tcm), in HCC. In addition, FAM49B expression was positively associated with immune checkpoints, immune regulation genes, MHC genes, chemokines and chemokine receptors. Patients with evaluated expression of FAM49B might be resistant to several anti-cancer drugs. Our results suggest that FAM49B is a potential prognostic biomarker for HCC. FAM49B play a potential key role in regulating tumor immune microenvironment and anti-tumor drug tolerance.

LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress

“…12C, http://links.lww.com/HEP/H887). A previous study showed that FAM49B upregulation was associated with poorer prognosis in patients with HCC 27 . To this end, we analyzed the clinical significance of LANCL1 and FAM49B co-expression.…”

“…A previous study showed that FAM49B upregulation was associated with poorer prognosis in patients with HCC. 27 To this end, we analyzed the clinical significance of LANCL1 and FAM49B co-expression. We defined high and low LANCL1 or FAM49B expression by T/NTL > 2 and T/NTL ≤ 2, respectively.…”

CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake

“…The Cyrib gene resides on human chromosome 8q24, near c-Myc, and is frequently amplified in many types of cancer, including pancreatic cancer ( Nikolaou and Machesky, 2020 ). High expression of CYRI-B correlates with poor outcome in many cancers ( Li et al, 2021 ; Xu et al, 2022a ), including in human pancreatic cancer. To further investigate a potential role for Cyrib in pancreatic cancer, we first assessed the expression of CYRI-B in the KPC mouse model of metastatic PDAC ( Hingorani et al, 2005 ).…”

CYRI-B mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake

“…The Cyri-b gene resides on human chromosome 8q24, near c-Myc, and is frequently amplified in many types of cancer, including pancreatic cancer (Nikolaou & Machesky, 2020). High expression of CYRI-B correlates with poor outcome in many cancers (Li et al , 2021; Xu et al , 2022a), including in human pancreatic cancer. To further investigate a potential role for cyri-b in pancreatic cancer we first assessed the expression of CYRI-B in the KPC mouse model of metastatic PDAC (Hingorani et al ., 2005).…”