Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified.

Methods: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort.

Early Diagnosis and Prognosis Prediction of Pancreatic Cancer Using Engineered Hybrid Core-Shells in Laser Desorption/Ionization Mass Spectrometry.

Effective detection of bio-molecules relies on the precise design and preparation of materials, particularly in laser desorption/ionization mass spectrometry (LDI-MS). Despite significant advancements in substrate materials, the performance of single-structured substrates remains suboptimal for LDI-MS analysis of complex systems. Herein, designer Au@SiO@ZrO core-shell substrates are developed for LDI-MS-based early diagnosis and prognosis of pancreatic cancer (PC).

Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.

Background: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive.

Methods: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile.

Modulation of cellular metabolism by protein crotonylation regulates pancreatic cancer progression.

Protein lysine crotonylation has been recently identified as a vital posttranslational modification in cellular processes, particularly through the modification of histones. We show that lysine crotonylation is an important modification of the cytoplastic and mitochondria proteins. Enzymes in glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, glutamine metabolism, glutathione metabolism, the urea cycle, one-carbon metabolism, and mitochondrial fusion/fission dynamics are found to be extensively crotonylated in pancreatic cancer cells.

Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips.

Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and revealed them as an unfavorable prognostic factor.

A Prognostic Nomogram for Hepatocellular Carcinoma Based on Wound Healing and Immune Checkpoint Genes.

Background And Aims: Wound healing and tumor progression share some common biological features; however, how variations in wound healing patterns affect hepatocellular carcinoma (HCC) prognosis remains unclear.

Methods: We analyzed the wound healing patterns of 594 HCC samples from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) and correlated them with immune infiltration and the expression levels of immune checkpoint genes. A risk score, which we named the "heal.

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations.

Liver metastases are common in pancreatic neuroendocrine tumors (PanNETs) patients and they are considered a poor prognostic marker. This study aims to analyze the spatiotemporal patterns of genomic variations between primary and metastatic tumors, and to identify the key related biomolecular pathways. We performed next-generation sequencing on paired tissue specimens of primary PanNETs ( = 11) and liver metastases ( = 12).

Inhibition of EGFR Overcomes Acquired Lenvatinib Resistance Driven by STAT3-ABCB1 Signaling in Hepatocellular Carcinoma.

Unlabelled: Lenvatinib is an inhibitor of multiple receptor tyrosine kinases that was recently authorized for first-line treatment of hepatocellular carcinoma (HCC). However, the clinical benefits derived from lenvatinib are limited, highlighting the urgent need to understand mechanisms of resistance. We report here that HCC cells develop resistance to lenvatinib by activating EGFR and stimulating the EGFR-STAT3-ABCB1 axis.

IL-6 Promotes Hepatocellular Carcinoma Invasion by Releasing Exosomal miR-133a-3p.

Interleukin-6 (IL-6), an important inflammatory cytokine, is a key factor regulating cancer metastasis. Cancer cells can modulate their tumorigenic abilities by sorting specific microRNAs (miRNAs) as exosomes into the tumor microenvironment. The relationship between IL-6 and exosomal miRNAs related to hepatocellular carcinoma (HCC) metastasis remains to be elucidated.

Subpopulations of cancer-associated fibroblasts link the prognosis and metabolic features of pancreatic ductal adenocarcinoma.

Background: Cancer-associated fibroblasts (CAFs) are a vital constituent of the tumor microenvironment (TME) and have several activities, but the effect of CAF heterogeneity on the molecular features and clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remains unknown.

Methods: An algorithm "scFrac" based on single-cell sequencing data from the Gene Expression Omnibus was introduced to emulate the enrichment of CAF subtypes in a TCGA-PDAC cohort and their prognostic influence, and confirmed by an external validation group (66 patients with PDAC) with multiplex immunohistochemistry staining. A comprehensive analysis including metabolic profile and transcription factor regulon activity was carried out among CAF subtypes.

Anatomical sites (Takasaki's segmentation) predicts the recurrence-free survival of hepatocellular carcinoma.

Background: Until now, several classification staging system and treatment algorithm for hepatocelluar carcinoma (HCC) has been presented. However, anatomical location is not taken into account in these staging systems. The aim of this study is to investigate whether anatomical sites could predict the postoperative recurrence of HCC patients.

Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3.

Intercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators.

The m6A methylation landscape stratifies hepatocellular carcinoma into 3 subtypes with distinct metabolic characteristics.

Objective: Epigenetic aberration plays an important role in the development and progression of hepatocellular carcinoma (HCC). However, the alteration of RNA N6-methyladenosine (m6A) modifications and its role in HCC progression remain unclear. We therefore aimed to provide evidence using bioinformatics analysis.

PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment.

Background And Aims: Pyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear.

Methods: GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both CCK-8, colony formation, and transwell assays, and xenografts were performed to evaluate the malignancy of HCC cells.

Isolation and characterization of exosomes for cancer research.

Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids.

Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer.

Enolase 2 (ENO2) is a key glycolytic enzyme in the metabolic process of glycolysis, but its potential function in pancreatic ductal adenocarcinoma (PDAC) is unclear. In this study, we observed a significant overexpression of ENO2 in PDAC tissues, and its expression was correlated with metastasis and poor prognosis in PDAC patients. K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity, cell metabolism and PDAC progression.

MFN1-dependent alteration of mitochondrial dynamics drives hepatocellular carcinoma metastasis by glucose metabolic reprogramming.

Background: Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear.

Methods: The mitochondrial fusion protein mitofusin-1 (MFN1) expression and its prognostic value are detected in HCC.

STMN1 upregulation mediates hepatocellular carcinoma and hepatic stellate cell crosstalk to aggravate cancer by triggering the MET pathway.

STMN1 has been regarded as an oncogene and its upregulation is closely associated with malignant behavior and poor prognosis in multiple cancers. However, the detailed functions and underlying mechanisms of STMN1 are still largely unknown in hepatocellular carcinoma (HCC) development. Herein, we analyzed STMN1 expression and the related clinical significance in HCC by using well-established Protein Atlas, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cancer databases.

A Novel Score Predicts HBV-Related Hepatocellular Carcinoma Recurrence After Hepatectomy: a Retrospective Multicenter Study.

Background: In China, hepatitis B virus (HBV) is an important causative factor of hepatocellular carcinoma (HCC). The contribution and interaction of fibrosis-4 (FIB-4) score and total tumor volume (TTV) in association with HCC recurrence is unknown. A reliable point score based on the FIB-4 score, TTV, and differentiation grade was established to predict the postoperative recurrence of HBV-related HCC patients who underwent hepatic resection (HR).