Cancer Liver Metastases Research Articles

M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4

RNA N6-methyladenosine (m6A) is a common RNA modification in eukaryotes, and its abnormal regulation is closely related to cancer progression. Aerobic glycolysis is a main way for cancer cells to obtain energy. It was found that beaded filament structural protein 1 (BFSP1) is a m6A related gene in liver cancer. However, the effect of m6A-modified BFSP1 on aerobic glycolysis and how it is regulated in liver cancer progression have not been explored. Here, we found that BFSP1 was upregulated in liver cancer cells and tissues. Overexpression of BFSP1 promoted the viability, invasion, and aerobic glycolysis of liver cancer cells, whereas knockdown of BFSP1 showed the opposite effects. Co-immunoprecipitation, immunofluorescence and GST pull down analyses showed that BFSP1 directly interacted with tropomodalin 4 (TMOD4), and knockdown of TMOD4 reversed BFSP1 overexpression-induced malignant phenotypes and aerobic glycolysis in liver cancer cells. Moreover, methyltransferase-like 3 (METTL3) enhanced BFSP1 stability by augmenting m6A modification of BFSP1 mRNA, which is achieved in a YTHDF1-dependent manner. In vivo experiments in mice confirmed that METTL3 increased BFSP1 stability by promoting m6A modification of BFSP1 mRNA, and knockdown of BFSP1 inhibited tumor growth and metastasis. In summary, METTL3-mediated m6A methylation of BFSP1 mRNA plays an important role in the aerobic glycolysis and progression of liver cancer, providing a potential therapeutic strategy for liver cancer.

NFAT2 Induces Tumor Cell Proliferation and Metastasis by Acting as a Transcriptional Co-activator of the TGF-β1/SMAD Signaling Pathway and Inducing the Epithelial-Mesenchymal Transition in Liver Cancer.

The role of NFAT2 in liver cancer is conflicting, with evidence suggesting both oncogenic and tumor-suppressive effects. A clear understanding of its expression, function, regulation, and mechanism of action in liver cancer remains critical. To examine the expression levels, biological functions, regulatory mechanisms, and downstream pathways of NFAT2 in liver cancer and its metastasis. The expression of NFAT2 was analyzed in liver cancer patients and correlated with clinical outcomes. Functional assays, including proliferation, migration, invasion, and xenograft models, were employed to assess the effects of NFAT2 upregulation and downregulation. Molecular analyses were conducted to identify key pathways and protein interactions underpinning NFAT2's effects. The therapeutic potential of NFAT2 inhibition in combination with sorafenib was also evaluated. NFAT2 overexpression was associated with poor prognosis and shorter disease-free survival in liver cancer patients. Upregulation of NFAT2 promoted hepatoma cell proliferation, migration, and invasion, while its downregulation impaired these pro-oncogenic effects. Mechanistically, NFAT2 enhanced the epithelial-to-mesenchymal transition (EMT) by increasing mesenchymal marker expression (N-cadherin, vimentin, MMP9) and decreasing invasion inhibitors (E-cadherin, ZO-1). It physically interacted with SMAD3 and p300, thereby activating the TGF-β1/SMAD pathway to drive tumor progression. NFAT2 knockdown or inhibition re-sensitized tumor cells to sorafenib, indicating its promising therapeutic potential. NFAT2 acts as a transcriptional co-activator of the TGF-β1/SMAD signaling pathway, promoting liver cancer progression and metastasis. Its inhibition could serve as a novel therapeutic strategy for the treatment of advanced liver cancer, particularly in combination with sorafenib.

Liver Metastasis in Cancer: Molecular Mechanisms and Management.

Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic-friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.

A novel 5-differentially expressed gene (DEG) signature predicting the prognosis in patients with metastatic liver malignancies and the prognostic and therapeutic potential of SPP1.

This study aimed to identify differentially expressed genes (DEGs) that are associated with hepatocarcinogenesis and metastasis in hepatocellular carcinoma (HCC) and to explore their value in predicting overall survival (OS). The methods used included bioinformatics analysis of gene expression datasets and in vitro experiments using HCC cell lines. Gene expression profiles from metastatic and non-metastatic liver cancer specimens were analyzed using the limma R package. Functional enrichment was performed using Metascape. A prognostic 5-gene signature was constructed using the LASSO algorithm based on TCGA-LIHC data. Kaplan-Meier survival analysis assessed the association of these genes with clinical outcomes (DFI, DSS, OS, and PFS). In vitro, Huh7 and Hep3B cells were transfected with shRNA for SPP1 knockdown. Cell viability was measured with CCK-8 assays, and migration was assessed with Transwell and wound-healing assays. Protein expression was evaluated via western blotting. The analysis of gene expression profiles led to the identification of 11 DEGs associated with immune response, phagocytosis, and cell migration. From these DEGs, the LASSO algorithm identified a 5-DEG signature (MASP1, MASP2, MUC1, TREM1, and SPP1) that was predictive of OS in liver cancer patients. Among the five genes, SPP1 was the most upregulated in cancer samples and was significantly associated with poorer outcomes, including DFI, DSS, OS, and PFS. In vitro experiments confirmed that SPP1 knockdown in Huh7 and Hep3B cells significantly inhibited cancer cell viability and migration. Western blot analysis showed alterations in key proteins, with a reduction in vimentin and Ki-67 and an increase in E-cadherin following SPP1 knockdown. This study highlights the pivotal effect of SPP1 on HCC development and underscores its potential as a biomarker for the OS of liver cancer patients. The identified DEGs may serve as predictive markers for OS and potential therapeutic targets for HCC treatment.

Neutrophil extracellular traps impede cancer metastatic seeding via protease-activated receptor 2-mediated downregulation of phagocytic checkpoint CD24

BackgroundPhagocytic clearance by macrophages represents a critical immune surveillance mechanism in cancer liver metastasis. Neutrophils, the most abundant immune cells encountered by cancer cells in circulation, play key roles in...

Transarterial Chemoembolization with BioPearls for the Treatment of Hepatocellular Carcinoma: A Preliminary Experience

Background/Objectives: Transarterial chemoembolization (TACE) is a widely accepted and minimally invasive treatment for primary and metastatic liver cancer. Performing TACE with drug-eluting beads helps obtain a greater drug concentration in the target lesion, significantly reducing systemic drug leakage, liver toxicity, and adverse events. The aim of this study is to describe the safety and feasibility of TACE performed with BioPearlTM, the first biodegradable drug-eluting microspheres. Methods: This was a retrospective observational study on 13 consecutive patients affected by hepatocellular carcinoma (HCC) treated with doxorubicin-loaded-BioPearlTM-TACE. Data on safety, feasibility, and tumor response were collected. Results: One intra-procedural catheter blockage was registered, as well as two post-treatment bilomas that required additional treatment. No severe general drug-related side effects were detected at the follow-up. The 1-month overall disease control was 90.9%, with six complete responses. Conclusions: Data suggest that chemoembolization with BioPearlTM is feasible and safe for the treatment of HCC as indicated by good tolerability.

CUEDC1 promotes the growth, migration, epithelial-mesenchymal transition and inhibits apoptosis of hepatocellular carcinoma cells via the TGF-β/Smad signaling pathway.

CUEDC1 promotes the growth, migration, epithelial-mesenchymal transition and inhibits apoptosis of hepatocellular carcinoma cells via the TGF-β/Smad signaling pathway.

The value and indications for surgery in pancreatic cancer with synchronous liver metastases.

714 Background: Over half of pancreatic cancer patients present with advanced disease and distant metastases, primarily in the liver, at initial diagnosis. Although systemic combination therapies have improved outcomes, the role of surgery remains contentious. This study seeks to pinpoint prognostic factors for patients with synchronous liver metastatic pancreatic cancer (sPDACLM) who receive effective treatments, and to identify patients likely to benefit from surgery. Methods: This is a retrospective cohort study. Included patients received first-line chemotherapy (AG/mFOLFIRINOX), with efficacy assessed every 4-6 cycles through imaging and biochemical evaluations. Imaging assessments were conducted according to RECIST 1.1 criteria, while biochemical evaluation focused on the reduction of CA19-9 (calculating cutoff values). Patients with good responses were considered for curative surgery, while those with minor responses decided between surgical treatment or continued maintenance therapy after being fully informed. Results: From May 2017 to February 2024, a total of 48 patients with sPDACLM who met the inclusion criteria were recruited for this study. The prognosis of patients with resectable or borderline resectable primary tumors was significantly superior to unresectable cases (18 months vs 11 months, p = 0.0011). Multivariate analysis revealed independent favorable prognostic factors: surgery (HR 0.22; p = 0.026), partial response (PR) per RECIST 1.1 criteria (HR 0.09, p = 0.040), and tumor marker reduction >85% (HR 27.99; p = 0.005). Achieving conversion effectiveness, as defined by imaging and biochemical criteria, was associated with a significantly improved prognosis compared to cases where conversion was ineffective (28 months vs. 12 months, p = 0.0086). Notably, effective surgery patients had a median survival of 49 months and a 5-year survival rate of 33%. Conversely, for patients who did not respond to systemic therapy, surgery did not confer any significant impact on overall survival; however, the corresponding survival curve indicated a trend towards shorter survival compared to those who did not undergo surgery. Conclusions: Patients with sPDACLM fulfill both imaging and biochemical criteria, exhibit improved prognoses; additionally, surgery has been shown to significantly prolong their median overall survival times. Research indicates that accurate screening for cases suitable for conversion surgery can significantly improve the survival rates of sPDACLM. Overall survival time and survival rates in patients with synchronous liver metastatic pancreatic cancer undergoing conversion therapy. OS 1-year survival rate 2-year survival rate 3-year survival rate 5-year survival rate Effective group Surgery 49 months 100% 88% 66% 33% Non-surgery 18 months 80% 20% - - Non-effective group Surgery 11 months 33% - - - Non-surgery 12 months 36% - - - OS, overall survival time.

Advances in Palmitoylation: A key Regulator of liver cancer development and therapeutic targets.

Advances in Palmitoylation: A key Regulator of liver cancer development and therapeutic targets.

Integrative Quantitative Analysis of Platelet Proteome and Site-Specific Glycoproteome Reveals Diagnostic Potential of Platelet Glycoproteins for Liver Cancer.

The role of peripheral blood platelets as indicators of cancer progression is increasingly recognized, and the significance of abnormal glycosylation in platelet function and related disorders is gaining attention. However, the potential of platelets as a source of protein site-specific glycosylation for cancer diagnosis remains underexplored. In this study, we proposed a general pipeline that integrates quantitative proteomics with site-specific glycoproteomics, allowing for an in-depth investigation of the platelet glycoproteome. With this pipeline, we generated a data set comprising 3,466 proteins with qualitative information, 3,199 proteins with quantitative information, 3,419 site-specific glycans with qualitative information and 3,377 site-specific glycans with quantitative information from peripheral blood platelets of hepatocellular carcinoma (HCC) patients, metastatic liver cancer (mLC) patients, and healthy controls. The integrated analysis revealed significant changes in platelet protein N-glycosylation in liver cancer patients. Further systems biology analysis and lectin pull-down-coupled ELISA assays in independent clinical samples confirmed two N-glycoproteins with specific glycan types, complement C3 (C3) with oligomannose modification and integrin β-3 (ITGB3) with sialylation, as potential biomarkers distinguishing liver cancer patients from healthy individuals, without differentiating between HCC and mLC patient group. These findings highlight the potential of platelet protein glycosylation as biomarkers.

Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer’s response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet. We found that Fulv treatment downregulates the ketogenesis pathway enzyme OXCT1, leading to β-hydroxybutyrate accumulation and decreased tumor cell viability. We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population.

Targeting BMP-1 enhances anti-tumoral effects of doxorubicin in metastatic mammary cancer: common and distinct features of TGF-β inhibition.

Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process. In addition, secretion of bone morphogenetic protein 1 (BMP-1), which is crucial for the proteolytic release of TGF-β, was markedly high in metastatic mammary cancer cells compared to non-metastatic cells. Although TGF-β inhibitors are in clinical trials, systemic inhibition of TGF-β may produce heavy side effects. We here hypothesize that inhibition of BMP-1 proteolytic activity inhibits TGF-β activity and induces anti-tumoral effects. Effects of specific BMP-1 inhibitor on liver and brain metastatic murine mammary cancer cells (4TLM and 4TBM), as well as on human mammary cancer MDA-MB-231 and MCF-7 cells, were examined and compared with the results of TGF-β inhibition. Inhibition of BMP-1 activity markedly suppressed proliferation of cancer cells and enhanced anti-tumoral effects of doxorubicin. Inhibition of BMP-1 activity but not of TGF-β activity decreased colony and spheroid formation. Differential effects of BMP-1 and TGF-β inhibitors on TGF-β secretion was also observed. These results demonstrated for the first time that the inhibition of BMP-1 activity has therapeutic potential for treatment of metastatic mammary cancer and enhances the anti-tumoral effects of doxorubicin.

The XIAP inhibitor AZD5582 improves the treatment effect of microwave ablation on hepatocellular carcinoma.

Microwave ablation (MWA) is one of the first-line therapy recommended for early-stage hepatocellular carcinoma (HCC). However, the residual tumor, resulting from insufficient ablation, led to recurrence and metastasis of liver cancer. Novel combination strategies are urgently needed to enhance efficiency of MWA. We detected the expression of XIAP protein after ablation in primary liver cancer patients using immunohistochemistry. Then, we established in vitro and in vivo IMWA models to further detect XIAP expression. We established an in vitro IMWA model by heating HCC cell lines and, at the same time, applied the XIAP inhibitor AZD5582 and verified the proliferation, migration, and pro-apoptotic ability of the XIAP inhibitor on tumor cells using CCK8, colony formation assay, cell scratch assay, and flow cytometry flow. The IMWA model of C57BL/6 and NTG mice were established, and AZD5582 was used in combination to evaluate the inhibitory and pro-apoptotic effects of different treatment regimens on tumor growth and to detect the local immune infiltration of C57BL/6 tumors. Finally, AZD5582 drug toxicity was detected to confirm its feasibility. XIAP protein expression is significantly increased in recurrent hepatocellular carcinoma tissues of patients who previously received microwave ablation therapy. In vitro experiments showed that the migration and proliferation ability of HCC cells was significantly reduced, and the level of apoptosis was increased after application of the XIAP inhibitor AZD5582. In vivo experiments further confirmed that ablation combined with the application of AZD5582 significantly reduced the proliferation ability of residual hepatocellular carcinoma. Concurrently, in C57 BL/6 mice with AZD5582 application, the level of local CD8+ T-cell infiltration in the tumor was increased, while the level of Foxp3+ regulatory T-cell infiltration was significantly reduced. The low toxicity of AZD5582 was further confirmed through hematological and pathological examinations of vital organs. These results provide new clues for hepatocellular carcinoma treatment, suggesting the potential role of XIAP inhibitors in hepatocellular carcinoma treatment and their impact in immunomodulation. In this study, we found that the XIAP inhibitor AZD5582 modulates the immune microenvironment and inhibits the progression of post-ablation residual hepatocellular carcinoma.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 4: Liver and locally recurrent rectal cancer

In this paper, we review the use of hypofractionated radiotherapy for gastrointestinal malignancies, focusing on primary and metastatic liver cancer, and recurrent rectal cancer. Technological advancements in radiotherapy have facilitated the direct delivery of high-dose radiation to tumors, while limiting normal tissue exposure, supporting the use of hypofractionation. Hypofractionated radiotherapy is particularly effective for primary and metastatic liver cancer where high-dose irradiation is crucial to achieve effective local control. For recurrent rectal cancer, the use of stereotactic body radiotherapy offers a promising approach for re-irradiation, balancing efficacy and safety in patients who have been administered previous pelvic radiotherapy and in whom salvage surgery is not applicable. Nevertheless, the potential for radiation-induced liver disease and gastrointestinal complications presents challenges when applying hypofractionation to gastrointestinal organs. Given the lack of universal consensus on hypofractionation regimens and the dose constraints for primary and metastatic liver cancer, as well as for recurrent rectal cancer, this review aims to facilitate clinical decision-making by pointing to potential regimens and dose constraints, underpinned by a comprehensive review of existing clinical studies and guidelines.

Role of Hep Par1 Immuno marker for Cytological Differentiation between Primary and Metastatic Liver Cancer

Space occupying lesions of liver is a major health problem worldwide. Among them the most important is malignant SOLs. Discrimination between primary HCC and metastatic tumor is extremely important for treating the patient. For this purpose immunocytochemical technique can be applied on fine needle aspiration samples. Among the various immunological markers, the role of Hepatocyte Paraffin 1 antibody (Hep Par 1) is found to be very much convincing for its higher sensitivity and specificity. To categorize the malignant lesions into primary and metastatic by immunocytochemistry, this cytomorphological study was done on patients of radiologically diagnosed space occupying lesions of liver. The study population comprised of benign and malignant hepatic SOL cases attending at Department of Pathology and Hepatology, DMCH over a period of two years (July 2017 to June 2019). The total number of samples was 100. Fine needle aspiration was done and cell block was prepared from residual material. Immunocytochemistry with Hep Par1 was applied on cell block material of malignant lesions. Cytomorphological and immunocytochemical findings of each cases were documented in details. The data were collected and statistical analysis was done by SPSS. The mean age of study patients were found 47.0±13.37 years in benign and 53.63±10.89 years in malignant group with age ranging from 26 to 78 years. Male to female ratio was 4:1. According to cytomorphology, 32(50.8%) cases were diagnosed as hepatocellular carcinoma, 25(39.7%) as metastatic adenocarcinoma, 1(1.6%) metastatic small cell carcinoma and 1(1.6%) metastatic spindle cell sarcoma. According to immunocytochemistry, diffuse cytoplasmic granular staining with Hep Par1 were found in 26(81.3%) and no staining was seen in 24(88.9%) cases. Sensitivity, specificity, PPV, NPV and accuracy of HepPar1 for detection of hepatocellular carcinoma were 100%, 80%, 81.25%, 100% and 89.29% respectively. HepPar1 in conjunction to cytology is a very useful diagnostic modality in differentiating HCC from metastatic tumor in suspicious cases.

Tumor exosomal RNPEP promotes lung metastasis of liver cancer via inducing cancer-associated fibroblast activation.

Cancer-associated fibroblasts (CAFs) are essential players in the tumor microenvironment (TME) due to their roles in facilitating tumor progression and metastasis. It is worth noting that the high-metastatic hepatocellular carcinoma (HCC) cell-derived exosomes have exhibited the ability to transform normal fibroblasts into CAFs, which further fosters the lung metastasis of low-metastatic HCC cells. Yet, the mechanisms underlying this tumor exosome-induced metastatic niche formation are poorly explored. In this study, the secreted protein arginyl aminopeptidase (RNPEP) was highly expressed in the plasma of patients with HCC. In addition, high-metastatic HCC cells showed augmented RNPEP expression levels in their exosomes. These exosomes induced obvious CAF-like properties in the human fibroblast cell line MRC-5, as evidenced by the increased CAF marker expression, and enhanced migratory ability. More strikingly, the secretions from high-metastatic tumor exosome-educated MRC-5 cells increased tumor stemness and promoted epithelial-mesenchymal transition (EMT) in MHCC-97L cells, a low-metastatic HCC cell line. However, the knockdown of RNPEP in exosomes from high-metastatic HCC cells abated the changes described above. Animal studies invivo highlighted the pro-tumor and pro-metastatic effects of exosomal RNPEP on MHCC-97L cells by inducing CAF activation. Furthermore, tumor-derived exosomal RNPEP induced the activation of NF-κB signaling in MRC-5 cells, a critical pathway associated with CAF activation. Collectively, these results provide novel insight into tumor-derived exosomal RNPEP for its crosstalk with CAFs during HCC lung metastasis.

Application of multiple inflammatory markers combined with PIVKA-II in differential diagnosis of AFP-NHCC

Alpha-fetoprotein (AFP) is a proven blood biomarker widely used in clinical detection of liver cancer, and its concentration increases immediately after liver injury, with high diagnostic specificity and low sensitivity. However, in patients with AFP-negative hepatocellular carcinoma (AFP-NHCC), also known as small liver cancer, their early stage of AFP expression is usually low or close to the normal range. Compared with AFP-positive HCC, AFP-NHCC is more likely to be subjected to missed diagnosis due to solely dependence on the measurement of blood AFP. Therefore, it is necessary to find a reliable, effective, and economical detection method for the early diagnosis of AFP-NHCC. PIVKA-II is closely related to the occurrence, development, invasion, and metastasis of liver cancer, and is also a new hematological marker widely used in the diagnosis of liver cancer in recent years. PIVKA-II effectively makes up for the limitation of negative AFP. 63.2% – 76.3% of patients with negative AFP showed positive PIVKA-II, and if only PIVKA-II detection was relied on, there would still be missed diagnosis in early patients with AFP-NHCC. In this retrospective study, we selected several commonly used inflammatory indicators to explore the diagnostic efficacy of PIVKA-II, an abnormal form of prothrombin, combined with inflammatory indicators in patients with early-stage AFP-NHCC and analyzed the relationship between some clinical features and hematological indicators in patients with AFP-NHCC. Serum levels of high-sensitivity C-reactive protein (hs-CRP), prealbumin (PA), neutrophil/lymphocyte ratio (NLR), and PIVKA-II were compared among three groups (AFP-NHCC group, benign lesion group, and healthy subjects). The diagnostic efficacy of PIVKA-II alone for AFP-NHCC and the diagnostic efficacy of three inflammatory indicators combined with PIVKA-II for AFP-NHCC were calculated, and their diagnostic specificity and sensitivity were compared. Compared with the other two groups, the AFP-NHCC group showed significant changes in three inflammatory markers and PIVKA-II, which may be related to the inflammatory progression of the tumor. Therefore, we recommend the establishment of a laboratory-based detection approach for diagnosing early-stage AFP-NHCC by combining PIVKA-II with inflammatory indicators hs-CRP, PA, and NLR, to facilitate diagnosis, treatment, and prognosis of AFP-NHCC.

Upregulation of ABLIM1 Differentiates Intrahepatic Cholangiocarcinoma from Hepatocellular Carcinoma and Both Colorectal and Pancreatic Adenocarcinoma Liver Metastases.

Altered gene expression in cancers holds great potential to improve the diagnostics and differentiation of primary and metastatic liver cancers. In this study, the expression of the protein-coding genes ring finger protein 135 (RNF135), ephrin-B2 (EFNB2), ring finger protein 125 (RNF125), homeobox-C 4 (HOXC4), actin-binding LIM protein 1 (ABLIM1) and oncostatin M receptor (OSMR) and the long non-coding RNAs (lncRNA) prospero homeobox 1 antisense RNA 1 (PROX1-AS1) and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) was investigated in hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and pancreatic ductal adenocarcinoma liver metastases. This study included 149 formalin-fixed, paraffin-embedded samples from 80 patients. After RNA isolation, quantification, reverse transcription and preamplification, real-time qPCR was performed. The gene expression between different groups was calculated relative to the expression of the reference genes using the ∆∆Cq method and statistically analyzed. The expression of the genes was additionally analyzed using the AmiCA and UCSC Xena platforms. In primary cancers, our results showed differential expression between primary tumors and healthy tissues for all the genes and lncRNA examined. Moreover, we found downregulation of RNF135 in hepatocellular carcinoma, downregulation of OSMR in colorectal liver metastases and upregulation of HOXC4 in cholangiocarcinoma compared to primary liver cancers and metastatic cancers. The major finding is the upregulation of ABLIM1 in cholangiocarcinoma compared to hepatocellular carcinoma, colorectal liver metastases, pancreatic ductal adenocarcinoma liver metastases and healthy liver tissue. We propose ABLIM1 as a potential biomarker that differentiates cholangiocarcinoma from other cancers and healthy liver tissue. This study emphasizes the importance of understanding the differences in gene expression between healthy tissues and primary and metastatic cancers and highlights the potential use of altered gene expression as a diagnostic biomarker in these malignancies.

Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization

The liver is the predominant metastatic site for diverse cancers, including pancreatic and colorectal cancers (CRC), etc. The high incidence of hepatic metastasis of pancreatic cancer is an important reason for its refractory and high mortality. Therefore, it is important to understand how metastatic pancreatic cancer affects the hepatic tumor immune microenvironment (TME) in patients. Here, we characterized the TME of liver metastases unique to pancreatic cancer by comparing them with CRC liver metastases. We integrated two single-cell RNA-seq (scRNA-seq) datasets including tumor samples of pancreatic cancer liver metastasis (P-LM), colorectal cancer liver metastasis (C-LM), primary pancreatic cancer (PP), primary colorectal cancer (PC), as well as samples of peripheral blood mono-nuclear cells (PBMC), adjacent normal pancreatic tissues (NPT), to better characterize the heterogeneities of the microenvironment of two kinds of liver metastases. We next performed comparative analysis on cellular compositions between P-LM and C-LM, found that Mph_SPP1, a subset of macrophages associated with angiogenesis and tumor invasion, was more enriched in the P-LM group, indicating this kind of macrophages provide a TME niche more vulnerable for pancreatic cancers. Analysis of the developmental trajectory implied that Mph_SPP1 may progressively be furnished with increased expression of genes regulating endothelium. Cell–cell communications analysis revealed that Mph_SPP1 potentially interacts with endothelial cells in P-LM via FN1/SPP1-ITGAV/ITGB1, implying this macrophage subset may construct an immunosuppressive TME for pancreatic cancer by regulating endothelial cells. We also found that Mph_SPP1 has a prognostic value in pancreatic adenocarcinoma that is not present in colon adenocarcinoma or rectum adenocarcinoma. This study provides a new perspective for understanding the characteristics of the hepatic TME in patients with liver metastatic cancer. And it provides a subset of macrophages specifically associated with the liver metastasis of pancreatic cancer, and its detection and intervention have potential value for preventing the metastasis of pancreatic cancer to the liver.

A new tumor-treating device OM-100 with low-frequency magnetic fields inhibits proliferation and metastasis in liver cancer

BackgroundThis study aims to investigate a novel instrument OM-100 with low-frequency magnetic fields (LFMFs) for its potential applicability in the treatment of liver cancer.MethodsLiver cancer cell lines (HepG2 and Huh7) and normal liver cell line THLE-2 were exposed to OM-100 at LFMFs of 0, 10, 25, 50, and 100 kHz for 2 h in the morning, noon, and evening, respectively. The effects of LFMF on cell viability, apoptosis, migration, and invasion capabilities were examined. Additionally, impacts of LFMF on ROS production was assessed. In vivo studies were conducted to examine the safety profile of OM-100 and its effects on tumor growth.ResultsIn vitro, OM-100 reduced the viability of liver cancer cells, increased cell apoptosis, and inhibited cell migration and invasion abilities in a frequency-dependent manner (P < 0.05). In vivo, OM-100 significantly slowed down tumor growth and promoted apoptosis in liver tumors (P < 0.05). Moreover, OM-100 rarely affected the viability of normal liver cells, as well as the health of normal mice. Finally, we further found that OM-100 significantly increased the production of ROS in liver cancer cells (P < 0.05), a key factor in inducing autophagy, which is very important for the progression of liver cancer.ConclusionOur findings reveal the safety of OM-100 and its frequency at 100 kHz significantly inhibits liver cancer progression.