Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

Purpose: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown.

Methods: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays.

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

Background And Aims: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI HCC and investigate the underlying immune infiltration patterns with radiomics features.

Methods: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis.

Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors.

CD36 cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor.

Hepatocellular carcinoma (HCC) is an immunotherapy-resistant malignancy characterized by high cellular heterogeneity. The diversity of cell types and the interplay between tumor and non-tumor cells remain to be clarified. Single cell RNA sequencing of human and mouse HCC tumors revealed heterogeneity of cancer-associated fibroblast (CAF).

Clinical Study on Systemic Lupus Erythematosus Complicated with Knee Bone Infarction.

Objective: The present study aims to (1) analyze the clinical characteristics and related influencing factors of knee bone infarction in systemic lupus erythematosus (SLE) and (2) improve the understanding of SLE complicated with knee bone infarction.

Methods: The data of patients with SLE complicated with knee bone infarction were retrospectively analysed; patients with SLE during the same period who matched in age, gender, and disease duration were selected as control subjects, with a 1 : 1 ratio with the SLE group. The clinical data were collected to analyze the risk factors for SLE complicated with knee bone infarction.

LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia.

Recently, the role of lncRNAs in tumorigenesis and development has received increasing attention, but the mechanism underlying lncRNAs-mediated tumor growth in the hypoxic microenvironment of solid tumors remains obscure. Using RNA sequencing, 25 hypoxia-related lncRNAs were found to be upregulated in HCC, of which lncRNA USP2-AS1 were significantly increased under hypoxia. We further confirmed that USP2-AS1 was significantly upregulated in liver cancer using FISH assay and that USP2-AS1 was associated with advanced liver cancer and increased tumor size.

MTDH antisense oligonucleotides reshape the immunosuppressive tumor microenvironment to sensitize Hepatocellular Carcinoma to immune checkpoint blockade therapy.

Immune checkpoint blockade (ICB) therapy is an important treatment option for individuals with cancer, but it has certain limitations. Identifying a better target that can overcome tumor immune escape and stimulate T cell activity is critical. This research aimed to delve into the molecular mechanism underlying the immunoregulatory function of metadherin (MTDH), which is a novel and potential therapeutic target in hepatocellular cancer (HCC).

Crosstalk Between Metabolism and Immune Activity Reveals Four Subtypes With Therapeutic Implications in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by metabolic dysregulation and distinct immunological signatures. The interplay between metabolic and immune processes in the tumor microenvironment (TME) causes the complexity and heterogeneity of immunotherapy responses observed during ccRCC treatment. Herein, we initially identified two distinct metabolic subtypes (C1 and C2 subtypes) and immune subtypes (I1 and I2 subtypes) based on the occurrence of differentially expressed metabolism-related prognostic genes and immune-related components.

Comprehensive analysis of tumor immune microenvironment and prognosis of m6A-related lncRNAs in gastric cancer.

Background: N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal roles in gastric cancer (GC) progression. The emergence of immunotherapy in GC has created a paradigm shift in the approaches of treatment, whereas there is significant heterogeneity with regard to degree of treatment responses, which results from the variability of tumor immune microenvironment (TIME). How the interplay between m6A and lncRNAs enrolling in the shaping of TIME remains unclear.

Risk stratification of LI-RADS M and LI-RADS 4/5 combined hepatocellular cholangiocarcinoma: prognostic values of MR imaging features and clinicopathological factors.

Objectives: To investigate the role of clinicopathological factors and MR imaging factors in risk stratification of combined hepatocellular cholangiocarcinoma (cHCC-CCA) patients who were classified as LR-M and LR-4/5.

Methods: We retrospectively identified consecutive patients who were confirmed as cHCC-CCA after surgical surgery in our institution from June 2015 to November 2020. Two radiologists evaluated the preoperative MR imaging features independently, and each lesion was assigned with a LI-RADS category.

Targeting HNRNPM Inhibits Cancer Stemness and Enhances Antitumor Immunity in Wnt-activated Hepatocellular Carcinoma.

Background & Aims: Cancer stemness and immune evasion are closely associated and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association.

Methods: The expressions of heterogeneous nuclear ribonucleoprotein M (HNRNPM) in 240 hepatocellular carcinoma (HCC) samples, public databases, and liver development databases were analyzed.

A multidimensional nomogram combining imaging features and clinical factors to predict the invasiveness and metastasis of combined hepatocellular cholangiocarcinoma.

Background: Combined hepatocellular cholangiocarcinoma (CHCC-CCA) is a rare type of primary liver cancer having aggressive behavior. Few studies have investigated the prognostic factors of CHCC-CCA. Therefore, this study aimed to establish a nomogram to evaluate the risk of microvascular invasion (MVI) and the presence of satellite nodules and lymph node metastasis (LNM), which are associated with prognosis.

Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study.

We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma-free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by next-generation sequencing before and after operation.

Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1.

Background: Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA.

Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma.

Background: Angiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated.

Methods And Results: Exosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively.

Profiles of alternative splicing landscape in breast cancer and their clinical significance: an integrative analysis based on large-sequencing data.

Background: Alternative splicing (AS) is closely correlated with the initiation and progression of carcinoma. The systematic analysis of its biological and clinical significance in breast cancer (BRCA) is, however, lacking.

Methods: Clinical data and RNA-seq were obtained from the TCGA dataset and differentially expressed AS (DEAS) events between tumor and paired normal BRCA tissues were identified.

Splicing factors: Insights into their regulatory network in alternative splicing in cancer.

More than 95% of all human genes are alternatively spliced after transcription, which enriches the diversity of proteins and regulates transcript and/or protein levels. The splicing isoforms produced from the same gene can manifest distinctly, even exerting opposite effects. Mounting evidence indicates that the alternative splicing (AS) mechanism is ubiquitous in various cancers and drives the generation and maintenance of various hallmarks of cancer, such as enhanced proliferation, inhibited apoptosis, invasion and metastasis, and angiogenesis.

Identification and validation of a new gene signature predicting prognosis of hepatocellular carcinoma patients by network analysis of stemness indices.

: Stem cells play an important role in hepatocellular carcinoma (HCC). However, their precise effect on HCC tumorigenesis and progression remains unclear. The present study aimed to characterize stem cell-related gene expression in HCC.

Genetic Alterations and Transcriptional Expression of mA RNA Methylation Regulators Drive a Malignant Phenotype and Have Clinical Prognostic Impact in Hepatocellular Carcinoma.

N6-methyladenosine (mA) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by the mA RNA regulators. However, its role in liver carcinogenesis is poorly understood. Three hundred seventy-one hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas database with sequencing and copy number variations/mutations data were included.

MACROD2 deficiency promotes hepatocellular carcinoma growth and metastasis by activating GSK-3β/β-catenin signaling.

Structural variations (SVs) influence the development and progression of multiple types of cancer. The genes affected by SVs in hepatocellular carcinoma (HCC) and their contribution to tumor growth and metastasis remain unknown. In this study, through whole-genome sequencing (WGS), we identified as the gene most frequently affected by SVs, which were associated with low MACROD2 expression levels.

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications.

Background: Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy.

Methods: A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed.

Comparative Effectiveness of Radiofrequency Ablation, Surgical Resection and Transplantation for Early Hepatocellular Carcinoma by Cancer Risk Groups: Results of Propensity Score-Weighted Analysis.

Purpose: Controversies exist for which treatment is optimal for early hepatocellular carcinoma (HCC): radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). We compared outcomes between treatments as first-line therapy for HCC patients measuring up to 5 cm or different cancer risk groups.

Patients And Methods: The Surveillance, Epidemiology, and End Results database was retrieved for HCC patients treated with RFA, SR, or LT between 2004 and 2015.