Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification DOI

Yuan Yue,

Jie Tao,

Dan An

et al.

The Journal of Gene Medicine, Journal Year: 2023, Volume and Issue: 26(1)

Published: Oct. 17, 2023

Abstract Background The current research investigated the heterogeneity of hepatocellular carcinoma (HCC) based on expression N7‐methylguanosine (m7G)‐related genes as a classification model and developed risk predictive HCC prognosis, key pathological behaviors molecular events HCC. Methods RNA sequencing data were extracted from Cancer Genome Atlas (TCGA)‐live cancer (LIHC) database, carcinoman database (HCCDB) Gene Expression Omnibus respectively. According to level 29 m7G‐related genes, consensus clustering analysis was conducted. least absolute shrinkage selection operator (LASSO) regression COX algorithm applied create prediction normalized five characteristic weighted by coefficients. Tumor microenvironment (TME) performed using MCP‐Counter, TIMER, CIBERSORT ESTIMATE algorithms. Immune Dysfunction Exclusion assess responses immunotherapy in different clusters groups. In addition, patient sensitivity common chemotherapeutic drugs determined biochemical half‐maximal inhibitory concentration R package pRRophetic. Results Three subtypes defined m7G‐associated each which had its specific survival rate, genomic variation status, TME status response. drug showed that C1 subtype more sensitive number conventional oncolytic (including paclitaxel, imatinib, CGP‐082996, pyrimethamine, salubrinal vinorelbine). five‐gene accurately predicted prognosis revealed degree somatic mutations, immune biological events. Conclusion this study, three heterogeneous model, created for predicting providing potential assessment tool understanding variation, mechanisms during development.

Language: Английский

Dendritic cell-derived exosome (DEX) therapy for digestive system cancers: Recent advances and future prospect DOI
Sulieman Ibraheem Shelash Al-Hawary, Yasir Q. Аlmajidi, Pooja Bansal

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 257, P. 155288 - 155288

Published: April 6, 2024

Language: Английский

Citations

1
Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response DOI Creative Commons

Jun Xue,

S. Yang, Si‐Si Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract Immunotherapies employing PD‐1/PD‐L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non‐responders to immunotherapy is imperative. Here, single‐cell‐scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) ICI‐treated PLC patients conducted, and tissue residence subpopulations assessed via multiplex immunohistochemistry. In the discovery cohort (n = 24), have lower baseline B cell HLA‐DR + CD8 T cell, higher CD14 CD16 − classical monocyte (CM) proportions. CMs decrease more in PBMCs, while conformably amplify after ICI‐exposure. Responsive individuals display upregulated exhaustion activation markers lineages. expanded 77 patients, augment re‐confirmed. Responders demonstrate much enrichment or tertiary lymphoid structures tumor compared non‐responders. A prospective model that excelled early discrimination developed using generalized linear achieves a satisfactory AUC over 0.9 all three independent cohorts. Integratedly, study unveils dynamic landscapes undergoing ICI‐based therapy, aiding patient stratification treatment fostering new monitoring strategies.

Language: Английский

Citations

1
The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression DOI Creative Commons
Zhongyuan Cui, Jielong Wang, Gang Chen

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 9, 2023

Patients with hepatocellular carcinoma (HCC) have poor prognosis, especially in advanced stages. Targeted therapy is the main treatment for HCC patients, but optimal targets remain poorly understood. The purpose of this study was to identify potential novel prognostic markers and therapeutic targets.Firstly, differentially expressed genes (DEGs) were identified from Gene Expression Omnibus (GEO) database. expression, significance mechanisms DEGs analyzed using GEPIA, TIMER, HPA, Kaplan Meier Plotter, CBioPortal, miRWalk, TargetScan, ENCORI databases. Immunohistochemical staining used determine protein expression levels candidate genes.The mRNA MND1, STXBP6, CLGN significantly increased (p< 0.01). patients elevated had poorer overall survival (OS), disease-free (DFS), progression-free (PFS), disease-specific (DSS) (p < 0.05). Higher MND1 correlated DFS However, there no significant correlation between STXBP6 prognosis (p> Further analysis revealed that pathology stages In addition, compared their normal tissues. abundance six common tumor infiltrating lymphocytes (COR 0.5). Moreover, mutation rate less than 1% (10/1089). Finally, level hsa-miR-194-3p lower tissues 0.05), low hsa-miR-194 0.05).The upregulation associated patient stages, may be regulated by hsa-miR-194-3p. These findings suggest closely related progression HCC, a target indicator HCC.

Language: Английский

Citations

3
A novel tumor 4-driver gene signature for the prognosis of hepatocellular carcinoma DOI Creative Commons
Houtian Guo, Fei Lu,

Rongqi Lu

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(6), P. e17054 - e17054

Published: June 1, 2023

Hepatocellular carcinoma (HCC), the main type of liver cancer, is second most lethal tumor worldwide, with a 5-year survival rate only 18%. Driver genes facilitate cancer cell growth and spread in microenvironment. Here, comprehensive driver gene signature for prognosis HCC was developed.HCC were analyzed comprehensively to develop better prognostic signature. The dataset patients included mRNA sequencing data clinical information from TCGA, ICGC, Guangxi Medical University Cancer Hospital cohorts. First, LASSO performed differentially expressed TCGA cohort. Then, robustness assessed using time-dependent ROC curves. Furthermore, independent predictors determined univariate multivariate Cox regression analyses. Stepwise multi-Cox analysis employed identify significant variables construction nomogram that predicts rates. Functional by Spearman correlation analysis, enrichment (GO, KEGG, GSEA), immunoassay (ssGSEA xCell) performed.A 4-driver (CLTC, DNMT3A, GMPS, NRAS) successfully constructed showed excellent predictive efficiency three indicated high accuracy 1-, 3-, prognoses patients, which risk score. Enrichment revealed involved regulating oncogenic processes, including cycle metabolic pathways, associated progression HCC. ssGSEA xCell differences immune infiltration microenvironment between two groups.The closely prediction expected provide new insights into targeted therapy patients.

Language: Английский

Citations

3
Case report: Predictability of clinical response and rejection risk after immune checkpoint inhibition in liver transplantation DOI Creative Commons
Jordi Yang Zhou,

Dominik Eder,

Florian Weber

et al.

Frontiers in Transplantation, Journal Year: 2023, Volume and Issue: 2

Published: Aug. 14, 2023

The approval of Atezolizumab / Bevacizumab therapy (Atezo/Bev) in 2020 opened up a promising new treatment option for patients with end-stage hepatocellular carcinoma (HCC). However, liver transplant (LTx) HCC are still denied this owing to concerns about ICI-induced organ rejection and lack regulatory approval.

Language: Английский

Citations

2
The alterations in peripheral lymphocyte subsets predict the efficacy and prognosis of immune checkpoint inhibitors in hepatocellular carcinoma DOI Creative Commons

Qu Xie,

Can Hu, Cong Luo

et al.

Journal of Cancer, Journal Year: 2023, Volume and Issue: 14(15), P. 2946 - 2955

Published: Jan. 1, 2023

Background: Immune checkpoint inhibitor (ICI) treatments are promising therapies for hepatocellular carcinoma (HCC) patients.However, not all HCC patients benefit from immunotherapy.Therefore, it is urgent to explore markers the clinical efficacy and prognosis of immunotherapy liver cancer.This study aimed investigate changes in peripheral blood lymphocyte subsets after assess their predictive prognostic value.Methods: Sixty-one with advanced were enrolled.Peripheral samples collected before ICI treatment, lymphocytes detected by flow cytometry.The rank sum test, chi-square Kaplan-Meier curve, Cox regression model used determine relationship between percentages clinicopathological characteristics, efficacy, progression-free survival (PFS) overall (OS).Results: After percentage CD3 + CD8 T cells increased, B decreased.The memory varied according different immune groups.Age, history hepatitis infection, first-line therapy, distant metastasis influenced proportion HCC.Furthermore, univariate analysis demonstrated that high natural killer (NK) change predicted longer PFS OS.Conclusions: treatment alters immunotherapy-treated patients.Changes variances immunological response features.A degree NK treated represents an independent predictor.

Language: Английский

Citations

2
Exploring potential predictive biomarkers through historical perspectives on the evolution of systemic therapies into the emergence of neoadjuvant therapy for the treatment of hepatocellular carcinoma DOI Creative Commons

Chuanlei Wang,

Wei Feng, Xiaodong Sun

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 27, 2024

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents third leading cause cancer-related deaths. Approximately half HCC patients miss opportunity for curative treatment are then limited to undergoing systemic therapies. Currently, therapy has entered era immunotherapy, particularly with advent immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes advanced HCC. Neoadjuvant become possibility—findings from IMbrave 050 trial indicated that ICIs offer benefit recurrence-free survival high-risk post-resection or local ablation. However, only small fraction individuals therapy. Consequently, there is an urgent need identify predictive biomarkers response outcome assessment. This study reviewed historical progression HCC, highlighting notable therapeutic advancements. examined development therapies involving conventional drugs clinical trials utilized in treatment, well potential and/or locally Various studies revealed context treatment. These include association dendritic cells (DCs) favorable neoadjuvant therapy, presence enriched T effector tertiary lymphoid structures, identification CD138+ plasma cells, distinct spatial arrangements B close proximity among responders receiving cabozantinib nivolumab Furthermore, pathological been associated intratumoral cellular triads consisting progenitor CD8+ CXCL13+ CD4+ helper surrounding mature DCs cemiplimab resectable Despite no widely recognized individualized we believe hold promise identifying validating them. because they can collect multiple samples across stages, especially multi-omics, bridging preclinical gaps.

Language: Английский

Citations

0
Machine learning and biomarkers in hepatocellular carcinoma: The future is now DOI Open Access
Francesca Romana Ponziani, Edoardo G. Giannini, Quirino Lai

et al.

Liver Cancer International, Journal Year: 2022, Volume and Issue: 3(3), P. 111 - 112

Published: Sept. 1, 2022

Language: Английский

Citations

2
Predictive Value of Peripheral Blood Markers in Hepatocellular Carcinoma Patients Treated with Anti-PD-1 in Combination with Targeted Therapy DOI Open Access
Shaodong Wang, Chengyou Du

Journal of Cancer Therapy, Journal Year: 2023, Volume and Issue: 14(04), P. 127 - 138

Published: Jan. 1, 2023

Background: There are currently no recognised biomarkers that identify predictive groups of benefit in patients with hepatocellular carcinoma receiving immune-combined targeted therapy, for which we explored the value peripheral blood markers as their prognosis. Methods: Patients who underwent anti-PD-1 combination therapy from 1 January 2019 to 31 December 2021 at First Affiliated Hospital Chongqing Medical University were retrospectively analysed. The data collected analysed by R software. Results: A total 41 cases included our study. optimal threshold values obtained plotting ROC curves and grouping patients. Survival analysis grouped showed statistically significant differences survival between different Platelet-lymphocyte ratio (PLR, P = 0.0022), Monocyte-lymphocyte (MLR, 0.042), Fibrinogen-Lymphocyte Ratio (FLR, 0.0009), Prognostic nutritional index (PIN, 0.0005), Fibrinogen-albumin (FAR, 0.0144). An ANOVA was performed on basic conditions groups, except difference BCLC stage (P 0.0128) high MLR low there age, gender, stage, hepatitis status groups. COX regression FAR, FLR PIN risk factors associated prognosis immunotherapy carcinoma, an independent factor carcinoma. Conclusions: We found promising predicting combined this study identified having advanced treated therapy.

Language: Английский

Citations

0
Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification DOI

Yuan Yue,

Jie Tao,

Dan An

et al.

The Journal of Gene Medicine, Journal Year: 2023, Volume and Issue: 26(1)

Published: Oct. 17, 2023

Abstract Background The current research investigated the heterogeneity of hepatocellular carcinoma (HCC) based on expression N7‐methylguanosine (m7G)‐related genes as a classification model and developed risk predictive HCC prognosis, key pathological behaviors molecular events HCC. Methods RNA sequencing data were extracted from Cancer Genome Atlas (TCGA)‐live cancer (LIHC) database, carcinoman database (HCCDB) Gene Expression Omnibus respectively. According to level 29 m7G‐related genes, consensus clustering analysis was conducted. least absolute shrinkage selection operator (LASSO) regression COX algorithm applied create prediction normalized five characteristic weighted by coefficients. Tumor microenvironment (TME) performed using MCP‐Counter, TIMER, CIBERSORT ESTIMATE algorithms. Immune Dysfunction Exclusion assess responses immunotherapy in different clusters groups. In addition, patient sensitivity common chemotherapeutic drugs determined biochemical half‐maximal inhibitory concentration R package pRRophetic. Results Three subtypes defined m7G‐associated each which had its specific survival rate, genomic variation status, TME status response. drug showed that C1 subtype more sensitive number conventional oncolytic (including paclitaxel, imatinib, CGP‐082996, pyrimethamine, salubrinal vinorelbine). five‐gene accurately predicted prognosis revealed degree somatic mutations, immune biological events. Conclusion this study, three heterogeneous model, created for predicting providing potential assessment tool understanding variation, mechanisms during development.

Language: Английский

Citations

0