Identification of PDCD1 and PDCD1LG2 as Prognostic Biomarkers and Associated with Immune Infiltration in Hepatocellular Carcinoma

Li, Wang; Mei, Mei; Liu, Tian; Zhang, Shuwen; Wang, Zeyu; Suo, Yuhong; Wang, Shuai; Liu, Yang; Lu, Wei

doi:10.2147/ijgm.s347163

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Disappointedly, emerging ICI immunotherapy has been shown to significantly improve clinical outcomes in HCC, but its objective response rate as monotherapy for HCC is only 15%–20% ( Ruf et al, 2021 ). Previous studies have shown that highly expressed PDCD1 has better OS and has a favorable relationship with CD8+ T cells, B cells, macrophages, CD4+ T cells ( Li et al, 2022 ). T cell immunoglobulin and ITIM domain protein (TIGIT) is a type I transmembrane protein, mainly expressed in activated T cells, Treg, memory T cells and NK cells.…”

Section: Discussionmentioning

confidence: 99%

EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma

Liu

Zhang

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis. It is urgent to find effective biomarkers. Eukaryotic Translation Initiation Factor 2 Subunit Beta (EIF2S2) is a subunit of heterotrimeric G protein EIF2, and its function is still unclear. We studied the role of EIF2S2 in the malignant progression of liver cancer and its relationship with immune infiltration.Methods: Download the RNA expression and clinical information of EIF2S2 from the Cancer Genome Atlas (TCGA) database, analyze the relationship between the expression of EIF2S2 and the prognosis and clinicopathological characteristics of HCC, analyze the differential genes by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and tumor related immune infiltrating cells. The Protein expression level of EIF2S2 was obtained from Human Protein Atlas (HPA) databases. The relationship between EIF2S2 expression and immune infiltrates in HCC was analyzed on TIMER 2.0. The data processing analysis based on R language. Drug Sensitivity data from Genomics of Drug Sensitivity in Cancer (GDSC).Results: EIF2S2 is highly expressed in HCC patients and is associated with poor prognosis. The expression of EIF2S2 was also correlated with age, clinical stage and pathological grade. Univariate and multivariate COX regression analysis showed that EIF2S2 was an independent risk factor for survival. The receiver operating characteristic (ROC) curve of EIF2S2 also confirmed the diagnostic value of EIF2S2 in HCC patients. Through GO and KEGG enrichment analysis, EIF2S2 expression was found to be closely related to some immune pathways. The expression of EIF2S2 was correlated with memory B cell, plasma B cell, CD8+ T cell, CD4+ resting memory T cell and the expression of some immune checkpoints, such as PDCD1, TIGIT and CTLA-4. It is also more sensitive to paclitaxel, sunitinib and other drugs.Conclusion: This study shows that EIF2S2 can be used as a prognostic factor for HCC, which is closely related to immune infiltration and immune checkpoints, and may play a potential regulatory role in predicting drug sensitivity.

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Section: Discussionmentioning

confidence: 99%

EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma

Liu

Zhang

et al. 2022

Front. Genet.

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Development and validation of a novel endoplasmic reticulum stress-related lncRNA signature in laryngeal squamous cell carcinoma

Pan,

Liu,

Xie

et al. 2024

Preprint

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Background Endoplasmic reticulum stress (ERS) is an intracellular process in which improperly folded proteins lead to a cellular stress response. Such responses serve to protect cells from damage and are tightly bound to the development and advancement of various tumors. How endoplasmic reticulum stress contributes to the onset and progression of laryngeal squamous cell carcinoma remains unclear. Our research aimed to find an ERS signature to forecast the prognosis of laryngeal squamous cell carcinoma and to investigate its potential biological functions. Method LSCC sample data obtained from The Cancer Genome Atlas (TCGA) database were co-expressed with ERS- related genes, and then a prognostic signature on the basis of endoplasmic reticulum stress- related lncRNAs (ERS-related lncRNAs) was constructed by differential analysis and Cox regression analysis. Survival analysis, TMB, consensus cluster analysis, drug sensitivity analysis, immune analysis and clinical drug prediction were carried out on the model. Finally, the function of LHX1-DT was verified by in vitro experiments. Results From the TCGA-LSCC cohort, 35 significantly different ERS-related lncRNAs were identified. Then, a prognostic signature consisting of three lncRNAs (AC110611.2, LHX1-DT, and AL157373.2) was identified. Kaplan-Meier analysis demonstrated the predictive ability of the model for overall survival. Calibration curves and receiver operating characteristic curves were validated and showed high predictive accuracy. Ultimately, the experimental results verified the expression of LHX1-DT in LSCC. Conclusion Our work built an ERS-related risk signature, providing a useful exegesis for LSCC prognosis prediction.

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Primary Resistance to Immunotherapy-Based Regimens in First Line Hepatocellular Carcinoma: Perspectives on Jumping the Hurdle

Salani

Genovesi

Vivaldi

et al. 2022

Cancers

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Immune checkpoint inhibitors (ICIs) are a key component of different stages of hepatocellular carcinoma (HCC) treatment, particularly in the first line of treatment. A lesson on the primary resistance which hampers their efficacy and activity was learned from the failure of the trials which tested them as first-line mono-therapies. Despite the combination of anti-PD(L)1 agents with anti-VEGF, anti CTLA4, or TKIs demonstrating relevant improvements in efficacy, the “doublets strategy” still shows room for improvement, due to a limited overall survival benefit and a high rate of progressive disease as best response. In this review, we discuss the results from the currently tested doublet strategies (i.e., atezolizumab+bevacizumab, durvalumab+tremelimumab with a mention to the newly presented ICIs/TKIs combinations), which highlight the need for therapeutic improvement. Furthermore, we examine the rationale and provide an overview of the ongoing trials testing the treatment intensification strategy with triplet drugs: anti-PD1+anti-CTLA4+anti-VEGF/TKIs and anti-PD1+anti-VEGF+alternative immunity targets. Lastly, we report on the alternative strategy to integrate ICIs into the new paradigm of immune therapeutics constituted by CAR-T and anti-cancer vaccines. This review provides up-to-date knowledge of ongoing clinical trials of the aforementioned strategies and critical insight into their mechanistic premises.

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Identification of PDCD1 and PDCD1LG2 as Prognostic Biomarkers and Associated with Immune Infiltration in Hepatocellular Carcinoma

Cited by 3 publications

References 24 publications

EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma

EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma

Development and validation of a novel endoplasmic reticulum stress-related lncRNA signature in laryngeal squamous cell carcinoma

Primary Resistance to Immunotherapy-Based Regimens in First Line Hepatocellular Carcinoma: Perspectives on Jumping the Hurdle

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