Inhibition of EPS8L3 suppresses liver cancer progression and enhances efficacy of sorafenib treatment

Chen, Bin; Pan, Yan; Xu, Xin; Wu, Fan; Zheng, Xuan; Chen, Siye; Zhao, Yuting; Huang, Zhou; Cheng, Sainan; Liu, Jianxiang; Wang, Weihu; Li, Yexiong

doi:10.1016/j.biopha.2020.110284

Cited by 9 publications

(9 citation statements)

References 22 publications

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“…This indicates that the addition of sorafenib treatment on top of TACE can effectively improve the QOL for patients with ALC. Immunity, also known as resistance, refers to the coordinated functioning of various systems in the human body under the control of the central nervous system to ensure the normal functioning of life activities [37]. The immune system is a crucial component of this coordination, with tissue barriers acting as the first line of defense of the immune system.…”

Section: Discussionmentioning

confidence: 99%

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

Zeng,

Yu,

Chen

et al. 2024

World J Surg Onc

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Objective The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). Methods 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. Results the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). Conclusion SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

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Section: Discussionmentioning

confidence: 99%

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

Zeng,

Yu,

Chen

et al. 2024

World J Surg Onc

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“…EPS8L3 is involved in the regulation of various cellular processes, including cell growth, proliferation and survival [ 35 ]. Although not reported in LUAD, its upregulation is associated with tumorigenesis and poor prognosis in patients with liver cancer, and can be used as a potential therapeutic target [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

Chen

Sun

et al. 2023

Aging

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Lung adenocarcinoma (LUAD) is the most common type of lung cancer which accounts for about 40% of all lung cancers. Early detection, risk stratification and treatment are important for improving outcomes for LUAD. Recent studies have found that abnormal accumulation of cystine and other disulfide occurs in the cell under glucose starvation, which induces disulfide stress and increases the content of disulfide bond in actin cytoskeleton, resulting in cell death, which is defined as disulfidptosis. Because the study of disulfidptosis is in its infancy, its role in disease progression is still unclear. In this study, we detected the expression and mutation of disulfidptosis genes in LUAD using a public database. Clustering analysis based on disulfidptosis gene was performed and differential genes of disulfidptosis subtype were analyzed. 7 differential genes of disulfidptosis subtype were used to construct a prognostic risk model, and the causes of prognostic differences were investigated by immune-infiltration analysis, immune checkpoint analysis, and drug sensitivity analysis. qPCR was used to verify the expression of 7 key genes in lung cancer cell line (A549) and normal bronchial epithelial cell line (BEAS-2B). Since G6PD had the highest risk factor of lung cancer, we further verified the protein expression of G6PD in lung cancer cells by western blot, and confirmed through colony formation experiment that interference with G6PD was able to significantly inhibit the proliferation ability of lung cancer cells. Our results provide evidence for the role of disulfidptosis in LUAD and provide new ideas for individualized precision therapy of LUAD.

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“…Although further clinical functional evaluation is still needed, some studies have shown the potential for mRNA development. For example, EPS8L3 has pivotal oncogenic functions in liver cancer, inhibition of EPS8L3 can prevent the progression of liver cancer and improve the e cacy of sorafenib treatment 20 . Furthermore, EPS8L3 depletion signi cantly inhibited cell proliferation and migration of liver cancer, and decreased the levels of phosphorylated PI3K and AKT in the PI3K/AKT signaling pathway 21 .…”

Section: Discussionmentioning

confidence: 99%

Dissecting Novel Tumor Antigens and Immune Subtypes Guided mRNA Vaccine Development for HBV Related-Hepatocellular Carcinoma

Lin

et al. 2022

Preprint

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The mRNA vaccines are considered to be effective treatment strategies for cancers, but its progress in chronic hepatitis B virus (HBV) related-hepatocellular carcinoma (HCC) was slow. This study aimed to find potential antigens and identify suitable patients in HBV related-HCC for guiding mRNA vaccine development. We integrated the transcriptome RNA expression matrices and somatic mutation data from TCGA and ICGC datasets. A consistency matrix was constructed by using ConsensusClusterPlus to identify the immune subtypes. Graph learning based dimensional reduction was analyzed to establish immune landscape. Four upregulated and mutated antigens (EPS8L3, TCOF1, EZH2, and NOP56) were highly correlated with unfavorable clinical outcomes and antigen presenting cells (APCs). And two distinct immune phenotypes with differential clinical, cellular, and molecular characteristics were identified by in the ICGC and TCGA cohorts. IS1 is immune “hot” and immunosuppressive phenotype, with low tumor mutation burden (TMB) and high immune checkpoints (ICPs). On the contrary, IS2 is immune “cold” phenotype with high TMB and low ICPs. Monocle3 package was used to further study the intra-cluster heterogeneity, which identified cluster IS2A/2B within IS2 subtype was determined to be more suitable for mRNA vaccine. In summary, EPS8L3, TCOF1, EZH2, and NOP56 are potential antigens for mRNA vaccine development against HBV related-HCC, and patients in IS2A/2B are relatively more suitable for vaccination.

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Inhibition of EPS8L3 suppresses liver cancer progression and enhances efficacy of sorafenib treatment

Cited by 9 publications

References 22 publications

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

Dissecting Novel Tumor Antigens and Immune Subtypes Guided mRNA Vaccine Development for HBV Related-Hepatocellular Carcinoma

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