Hepatocellular carcinoma-specific epigenetic checkpoints bidirectionally regulate the antitumor immunity of CD4 + T cells.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with significant global health implications. The role of CD4 T cells, particularly conventional CD4 T cells (Tconvs), in HCC progression remains unexplored. Furthermore, epigenetic factors are crucial in immune regulation, yet their specific role in HCC-infiltrating Tconv cells remains elusive.

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis.

Lysine methylation modifications in tumor immunomodulation and immunotherapy: regulatory mechanisms and perspectives.

Lysine methylation is a crucial post-translational modification (PTM) that significantly impacts gene expression regulation. This modification not only influences cancer development directly but also has significant implications for the immune system. Lysine methylation modulates immune cell functions and shapes the anti-tumor immune response, highlighting its dual role in both tumor progression and immune regulation.

Moderate Ischemic Mitral Regurgitation with Ejection Fraction <40% Undergoing Concomitant Mitral Valve Repair during Revascularization: A Single-Center Observational Study.

Background: Numerous studies have examined the therapeutic effects of mitral valve repair during revascularization on moderate ischemic mitral regurgitation (IMR), as well as the incremental benefit of subvalvular repair alongside an annuloplasty ring. However, the impact of depressed left ventricular (LV) function on the surgical outcome of patients with moderate IMR has been rarely investigated. The aims of this single-center, retrospective, observational study were firstly to evaluate short- and medium-term outcomes in this patient group after undergoing mitral valve repair during revascularization, and secondly to assess the impact of depressed LV function on surgical outcomes.

SOX12 Facilitates Hepatocellular Carcinoma Progression and Metastasis through Promoting Regulatory T-Cells Infiltration and Immunosuppression.

Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T-cell (Treg) infiltration, decreases CD8T-cell infiltration, and hastens HCC metastasis.

Deciphering the roles of the HMGB family in cancer: Insights from subcellular localization dynamics.

The high-mobility group box (HMGB) family consists of four DNA-binding proteins that regulate chromatin structure and function. In addition to their intracellular functions, recent studies have revealed their involvement as extracellular damage-associated molecular patterns (DAMPs), contributing to immune responses and tumor development. The HMGB family promotes tumorigenesis by modulating multiple processes including proliferation, metabolic reprogramming, metastasis, immune evasion, and drug resistance.

Context-dependent T-BOX transcription factor family: from biology to targeted therapy.

T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments.

The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma.

In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver.

Prediction model of pressure injury occurrence in diabetic patients during ICU hospitalization--XGBoost machine learning model can be interpreted based on SHAP.

Background: The occurrence of pressure injury in patients with diabetes during ICU hospitalization can result in severe complications, including infections and non-healing wounds.

Aims: The aim of this study was to predict the occurrence of pressure injury in ICU patients with diabetes using machine learning models.

Study Design: In this study, LASSO regression was used for feature screening, XGBoost was employed for machine learning model construction, ROC curve analysis, calibration curve analysis, clinical decision curve analysis, sensitivity, specificity, accuracy, and F1 score were used for evaluating the model's performance.

Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment.

High-throughput and proteome-wide discovery of endogenous biomolecular condensates.

Phase separation inside mammalian cells regulates the formation of the biomolecular condensates that are related to gene expression, signalling, development and disease. However, a large population of endogenous condensates and their candidate phase-separating proteins have yet to be discovered in a quantitative and high-throughput manner. Here we demonstrate that endogenously expressed biomolecular condensates can be identified across a cell's proteome by sorting proteins across varying oligomeric states.

TGF-β1-Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis Through Transcriptionally Upregulating PD-L1 and CXCL12.

Background & Aims: Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis, and immunotherapy resistance. Identification of HCC-intrinsic factors regulating the immunosuppressive microenvironment is urgently needed. Here, we aimed to elucidate the role of SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression and to validate novel combination strategies for SOX18-mediated HCC progression and metastasis.

SOX on tumors, a comfort or a constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors.

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development.

Pan-cancer analysis of ABCC1 as a potential prognostic and immunological biomarker.

ABCC1 belongs to the ATP-binding cassette (ABC) superfamily, which encompasses a total of 48 constituent members. ABCC1 has been shown to be associated with the growth, progression, and drug resistance of various types of cancer. However, the impact of ABCC1 on cancer immune infiltration and pan-cancer prognosis has been rarely studied.

Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8 T cell-mediated antitumour immunity and improves anti-PD-1 efficacy.

Objective: The gain of function (GOF) CTNNB1 mutations (CTNNB1 ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC.

Design: RNA sequencing was performed to identify the key downstream genes of CTNNB1 associated with immune escape.

SRSF10 facilitates HCC growth and metastasis by suppressing CD8T cell infiltration and targeting SRSF10 enhances anti-PD-L1 therapy.

Background And Aims: RNA splicing is an essential step in regulating the gene posttranscriptional expression. Serine/arginine-rich splicing factors (SRSFs) are splicing regulators with vital roles in various tumors. Nevertheless, the expression patterns and functions of SRSFs in hepatocellular carcinoma (HCC) are not fully understood.

LINC01980 induced by TGF-beta promotes hepatocellular carcinoma metastasis via miR-376b-5p/E2F5 axis.

Hepatocellular carcinoma (HCC) is one of the most aggressive human malignancies worldwide. However, the molecular mechanism of HCC metastasis is largely unknown. Long non-coding RNA (lncRNA) plays a key role in gene regulation, and dysregulation of lncRNA is critical to cancer metastasis.

HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2.

Metastasis is a major cause of HCC-related deaths with no effective pharmacotherapies. Chronic inflammation promotes HCC dissemination, however, its underlying mechanisms are not fully understood. Here, we investigated the role of Krüppel-like factor 7 (KLF7) in inflammation-provoked HCC metastasis and proposed therapeutic strategies for KLF7-positive patients.

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC.

Metastasis accounts for the high lethality of colorectal cancer (CRC) patients. Unfortunately, the molecular mechanism manipulating metastasis in CRC is still elusive. Here, we investigated the function of E74-like factor 4 (ELF4), an ETS family member, in facilitating CRC progression.

FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2.

Background & Aims: Metastasis remains the major reason for the high mortality of patients with hepatocellular carcinoma (HCC). This study was designed to investigate the role of E-twenty-six-specific sequence variant 4 (ETV4) in promoting HCC metastasis and to explore a new combination therapy strategy for ETV4-mediated HCC metastasis.

Methods: PLC/PRF/5, MHCC97H, Hepa1-6, and H22 cells were used to establish orthotopic HCC models.

An integrative analysis revealing cuproptosis-related lncRNAs signature as a novel prognostic biomarker in hepatocellular carcinoma.

Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive. We obtained patients' RNA expression data and follow-up information from University of California Santa Cruz (UCSC) and The Cancer Genome Atlas (TCGA). We analyzed the mRNA level of Cuproptosis-related genes (CRGs) and performed univariate Cox analysis.

ETS transcription factors: Multifaceted players from cancer progression to tumor immunity.

The E26 transformation specific (ETS) family comprises 28 transcription factors, the majority of which are involved in tumor initiation and development. Serving as a group of functionally heterogeneous gene regulators, ETS factors possess a structurally conserved DNA-binding domain. As one of the most prominent families of transcription factors that control diverse cellular functions, ETS activation is modulated by multiple intracellular signaling pathways and post-translational modifications.

Identification of necroptosis-related subtypes, development of a novel signature, and characterization of immune infiltration in colorectal cancer.

Introduction: Necroptosis, a type of programmed cell death, has recently been extensively studied as an important pathway regulating tumor development, metastasis, and immunity. However, the expression patterns of necroptosis-related genes (NRGs) in colorectal cancer (CRC) and their potential roles in the tumor microenvironment (TME) have not been elucidated.

Methods: We explored the expression patterns of NRGs in 1247 colorectal cancer samples from genetics and transcriptional perspective.