Multiomics in silico analysis identifies TM4SF4 as a cell surface target in hepatocellular carcinoma
Kah Keng Wong, Suzina Sheikh Ab. Hamid, Mahmood S Choudhery, Mahmood S Choudhery, Mahmood S Choudhery
TL;DR
This study identifies TM4SF4 as a potential cell surface target for treating hepatocellular carcinoma with reduced toxicity to normal tissues.
Contribution
TM4SF4 is proposed as a novel cell surface target for HCC immunotherapy with favorable expression profiles and oncogenic associations.
Findings
TM4SF4 showed significantly higher expression in HCC compared to seven other common HCC targets.
TM4SF4 is absent in immune cells and expressed in hepatocyte regions inaccessible to immune cells.
TM4SF4 expression correlates with mitochondrial and oxidative phosphorylation pathways in HCC cells.
Abstract
The clinical application of cellular immunotherapy in hepatocellular carcinoma (HCC) is impeded by the lack of a cell surface target frequently expressed in HCC cells and with minimal presence in normal tissues to reduce on-target, off-tumor toxicity. To address this, an in silico multomics analysis was conducted to identify an optimal therapeutic target in HCC. A longlist of genes (n = 12,948) expressed in HCCs according to The Human Protein Atlas database were examined. Eight genes were shortlisted to identify one with the highest expression in HCCs, without being shed into circulation, and with restrictive expression profile in other normal human tissues. A total of eight genes were shortlisted and subsequently ranked according to the combination of their transcript and protein expression levels in HCC cases (n = 791) derived from four independent datasets. TM4SF4 was the top-ranked…
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Taxonomy
TopicsCancer Immunotherapy and Biomarkers · Immunotherapy and Immune Responses · Ferroptosis and cancer prognosis