Cancer Liver Metastases Research Articles

Ruangan Lidan decoction inhibits the growth and metastasis of liver cancer by downregulating miR-9-5p and upregulating PDK4

ABSTRACT A growing number of studies have suggested that traditional Chinese medicine (TCM) plays an essential role in the development and occurrence of liver cancer. However, the function of Ruangan Lidan decoction (RLD) in liver cancer are not yet adequately identified and manifested, which attracted our attention. The key genes related to liver cancer and RLD and the upstream miRNAs of PDK4 were obtained based on bioinformatics analysis, followed by verification of the targeting relationship between miR-9-5p and PDK4. Next, Huh7 cells were treated with RLD to detect cell proliferation, colony formation, migration, invasion, and apoptosis by multiple assays with gain- and loss-of-function experiments. Moreover, subcutaneous transplanted tumor model and lung metastasis model of liver cancer in nude mice were established to further verify the functional role of RLD in liver cancer growth and metastasis via miR-9-5p/PDK4 axis. Bioinformatics analysis found that PDK4 and miR-9-5p were related to liver cancer, and PDK4 may be a downstream regulator of RLD. miR-9-5p could target and inhibit PDK4. In vitro cell experiments demonstrated that RLD suppressed liver cancer cell proliferation, invasion and migration, and promoted apoptosis by inhibiting miR-9-5p expression and promoting PDK4 expression. In vivo animal experiments further confirmed that RLD inhibited liver cancer growth and metastasis via upregulation of miR-9-5p-dependent PDK4. RLD downregulated miR-9-5p and upregulated PDK4 to inhibit the proliferation, migration, invasion, and induce apoptosis, thereby suppressing the growth and metastasis of liver cancer, highlighting a potential novel target for treatment of liver cancer.

Salvage Radiotherapy Improves Survival in Patients with Metastatic Liver Cancer after Immunotherapy Oligoprogression

Immune checkpoint inhibitors (ICIs) have ameliorated the survival outcome of liver cancer, a majority of patients receiving ICIs have eventually developed progression. Local therapy, especially radiotherapy (RT), is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy. The aim of this study was to evaluate the efficacy and safety of RT as a salvage treatment in patients with oligoprogression after ICIs. This retrospective study was performed to evaluate the use of salvage radiotherapy in oligoprogressive metastatic liver cancer patients. Patients with metastatic liver cancer who had previous stability or response after ≥ 6 mo of ICIs were eligible if they developed progression of five of fewer metastases. Overall, 178 patients treated between August 2018 and March 2022 were included. The patients were followed for a median of 17.2 months. The overall response rate (ORR) and disease control rate (DCR) were 38.2% and 57.8%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.5 (95% CI:5.116-7.884) and 17.3 (95% CI:11.166-23.434) months. In multivariate analysis, factors associated with OS included tumor size, tumor number, and radiated tumor site (intrahepatic vs. extrahepatic). The most frequent AEs were fatigue, decreased appetite, rash, fever, and nausea. The above-mentioned AEs were reversible and manageable. Salvage radiotherapy has a potential activity and is tolerable for oligoprogression after ICIs with appropriate radiated tumor site and patient selection. A prospective randomized trial is ongoing to validate this finding (ChiCTR2200060664).

Statistical Analysis to Determine the Predictors of Liver Segmental Hypertrophy Observed Post-Radiotherapy

Prediction of liver segment hypertrophy based on radiotherapy (RT) dose is crucial for maximizing functional liver volume and avoiding hepatic failure after RT. We determined predictors associated with liver hypertrophy with stratification based on induction chemo (IC) and tumor location. RT planning, CT images, and 3-month-followup CTs were analyzed from 148 patients who underwent RT for primary or metastatic liver cancers. A nnUNet based model was trained (train/test = 160/40 CTs) to contour the liver segments (1, 2, 3, 4, 5-8) with accuracy assessed using Dice Similarity Coefficients (DSC). 52 features corresponding to segments 1, 2, 3, 2+3, 4, 5-8, were collected including equivalent dose to 2Gy fractions metrics-mean dose (Dmean), dose received by 95% of the volume (D95), volume spared from x gy (Vx), cancer type, tumor location, and IC status. Descriptive statistics were reported as percentage of segments showing hypertrophy under all stratification. Predictors were compared with 6 response variables using Chi-squared/Fisher-Exact test (CST/FET) and logistic regression (LR) for categorical and numerical predictors. The nnUNet model had an average DSC of 0.91 across all segments. Overall, segments 1, 4, and 5-8 showed hypertrophy in 35% of cases, and segments 2, 3 and 2+3 showed hypertrophy in 45-49% of patients. Stratification based on tumor location resulted in segment 2+3 hypertrophy in 66% of patients when the tumor was in segments 5-8. For bilobed tumors, segment 2+3 hypertrophy was observed in 34% of patients. CST/FET showed that tumor location, IC, and tumor type were significant predictors of segment 5-8 hypertrophy. Tumor location was also a significant predictor of segments 3 and 2+3 hypertrophy. In LR analysis, all segment-based dose metrics were significant predictors of segment hypertrophy except Dmean in segment 4, and D95 in segment 2 and 4. Overall, the strongest association was obtained for V35 significantly predicting for each segment hypertrophy. The mean dose for segments with hypertrophy was significantly lower (range: 15-30 Gy) than segments with atrophy (p<0.01), except for segment 4 where the mean dose was 10Gy lower but did not reach significance. IC impacts the threshold mean dose that leads to hypertrophy, with more toxic drugs reducing the mean dose threshold. Tumor location and IC significantly impact the response of segments to RT. Dose volume metrics are strong predictors of volumetric response with segment volume spared from 35 Gy being the strongest predictor.

Radiotherapy for Liver Cancer: An International Multi-Centre Pooled Analysis of 925 Cases

Primary and secondary liver cancer incidence is growing and has a poor prognosis. The standard use of radiation has been hampered by studies with a wide range of patients, different management protocols and varied outcomes. To overcome this heterogeneity in the literature, larger and higher-level trials are warranted, but, so far, have been difficult to implement. Therefore, pooled analyses may offer the best way to determine the benefit of radiation, identify treatment parameters needed to optimize treatment techniques, and identify patient factors that allow for better patient selection. Patients with liver cancer treated by radiotherapy at centers in Canada, United States and Australia was pooled. Patient and treatment characteristics were noted, as well as the clinical outcomes of local control within 1 year, recurrence and mortality. Stepwise Cox proportional hazards models were used to identify significant predictors for recurrence and mortality. Patients were stratified by center, and primary versus metastatic disease. A total of 925 patients were included in this study. Mean age was 67 years, and 45% had a primary diagnosis of hepatocellular carcinoma. 1-year local control rate was 80%. Median survival was 1.8 years (1.9 years for primary liver cancer, and 1.4 years for metastatic liver cancer). Higher total dose and BED was associated with better survival. Median time to recurrence was 1.5 years. Higher total dose was associated with lower risk of recurrence CONCLUSION: As one of the largest pooled analyses in hepatic cancer, this international multi-center study provides pragmatic data on clinical outcomes of patients receiving radiotherapy for liver cancer. This database may assist in better selection of patients for future studies and answer questions such as what is the optimal dose and which patients benefit from treatment.

Comparative proteomic profiling of plasma exosomes in lung cancer cases of liver and brain metastasis

BackgroundMetastases within liver or the brain are the most common causes of mortality from lung cancer (LC). Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging but important for early patient intervention. According to mounting evidence, exosomes circulating within blood may facilitate cancer spread by transporting certain proteins for target cells.MethodsUsing liquid chromatography–MS/MS, we investigated the plasma exosomes’ proteomic profiles derived from 42 metastatic LC patients [16 solitary liver metastasis (LM), together with 26 solitary brain metastasis (BM)] and 25 local advanced (LA) lung cancer cases without metastasis, together with five healthy controls (HC), assessing the LM and BM pathogenesis and find potential novel organ-designated proteomic biomarkers. Using ELISA assay, we verified the expression levels of three plasma exosomal protein biomarkers in 110 LC patients, including 40 solitary LM, 32 solitary BM and 38 LA, and 25 HC.ResultsIn total, 143 and 120 differentially expressed exosome-based proteins (DEEPs) were found to be dysregulated in LM and BM of lung cancer (LM-DEEPs, BM-DEEPs), compared for LA lung cancer samples, respectively. The bioinformatics analyses indicated the heterogeneity and homogeneity in LM-DEEPs and BM-DEEPs. They were primarily engaged within proteomic triggering cascade, ECM-receptor interaction, and the collagen-containing extracellular matrix. Regarding heterogeneity, LM-DEEPs primarily consisted of proteoglycans, lipoprotein, integrin, and heat shock protein, whereas the BM-DEEPs consisted of calcium-dependent/S100 proteins. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)-plasma-stemming exosome proteomics showed heterogeneity, which helped to explain some of the differences between SCLC and NSCLC's metastatic features. We also found that SELL and MUC5B could be used as diagnostic markers of BM, while APOH, CD81, and CCT5 could help diagnose LM in LC patients. Additionally, we demonstrated in a validation cohort that MUC5B and SELL could serve as biomarkers for diagnosing BM, and APOH could be a novel potential diagnostic biomarker of LM.ConclusionWe presented the comprehensive and comparative plasma-stemming exosomes’ proteomic profiles from cases of LC who had isolated liver and brain metastases for the first time. We also suggested several possible biomarkers and pathogenic pathways that might be a great starting point for future research on LC metastasis.

A Booster for Radiofrequency Ablation: Advanced Adjuvant Therapy via In Situ Nanovaccine Synergized with Anti-programmed Death Ligand 1 Immunotherapy for Systemically Constraining Hepatocellular Carcinoma.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for treating hepatocellular carcinoma (HCC), which could destroy tumors through hyperthermia and generate massive tumor-associated antigens (TAAs). However, residual malignant tissues or small satellite lesions are hard to eliminate, generally resulting in metastases and recurrence. Herein, an advanced in situ nanovaccine formed by layered double hydroxides carrying cGAMP (STING agonist) (LDHs-cGAMP) and adsorbed TAAs was designed to potentiate the RFA-induced antitumor immune response. As-prepared LDHs-cGAMP could effectively enter cancerous or immune cells, inducing a stronger type I interferon (IFN-I) response. After further adsorption of TAAs, nanovaccine generated sustained immune stimulation and efficiently promoted activation of dendritic cells (DCs). Notably, infiltrations of cytotoxic lymphocytes (CTLs) and activated DCs in tumor and lymph nodes were significantly enhanced after nanovaccine treatment, which distinctly inhibited primary, distant, and metastasis of liver cancer. Furthermore, such a nanovaccine strategy greatly changed the tumor immune microenvironment and promoted the response efficiency of anti-programmed death ligand 1 (αPD-L1) immunotherapy, significantly arresting the poorly immunogenic hepa1-6 liver cancer progression. These findings demonstrate the potential of nanovaccine as a booster for RFA in liver cancer therapy and provide a promising in situ cancer vaccination strategy.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy, including primary liver cancer and metastatic liver cancer, has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy. Radioembolization with yttrium-90 (90Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy. The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with 90Y microspheres, from patient selection to follow up, both technically and clinically, are discussed in this paper. It describes the application and development of 90Y microspheres in the treatment of liver cancer.

Retraction Note: HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail

Retraction Note: HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail

N-glycosylation at N57/100/110 affects CD44s localization, function and stability in hepatocellular carcinoma

The glycosylation levels of proteins in cancer cells are closely related to cancer invasion and migration. CD44 is a transmembrane glycoprotein that is significantly overexpressed in a variety of tumor cells and has been proven to promote the migration and motility of cancer cells, but the effect of its N-glycosylation modification on CD44 protein function in tumors is less studied. Here, we investigated the effect of six N-glycan chains (N25/57/100/110/120/255) on CD44s localization, function and stability in hepatocarcinoma cells. When the six sites were mutated, we found that CD44s lost its membrane localization in Huh7 and MHCC-97H cells. On this basis, we identified three glycosylation sites on CD44s (N57, N100 and N110) that played key roles in intracellular localization. When N57, N100 and N110 were mutated together, CD44 localized to the cytoplasm, while another three-site mutant (N25/N120/N255) was still anchored to the membrane. In addition, the ability of CD44-N57Q/N100Q/N110Q to promote the metastasis and invasion of Huh7 and 97H cells was weakened compared with that of CD44-N25Q/N120Q/N255Q. Furthermore, CD44-N57Q/N100Q/N110Q accumulated abnormally in the ER, and a high level of the ER stress (ERS) marker BiP was detected at the same time compared with wild-type CD44. When the lysosome inhibitor CQ was added, the content of mutant protein that triggered ERS significantly increased, which indicated that the degradation mode of CD44-N57Q/N100Q/N110Q after ERS was mainly through the lysosomal pathway (ERLAD). The results revealed that the N-glycosylation sites N57, N100 and N110 mutated on CD44s affected its function and degraded it by lysosomes after triggering ERS. These findings provide data for new studies on ER-related degradation, further promote the study of the glycan chain function of CD44 and furnish new ideas for the treatment of liver cancer metastasis.

Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer.

Metastasis is a fatal status for liver cancer, and the identification of an effective prediction model and promising therapeutic target is essential. Given the known relationship between fatty acid (FA) metabolism and the liver, the present study aimed to investigate dysregulation of genes associated with FA metabolism in liver cancer. Bioinformatics analyses were performed on data from patients with hepatocellular carcinoma (HCC) obtained from The Cancer Genome Atlas database using R software packages. Online public tools such as the Human Protein Atlas, Tumor Immune Single-Cell Hub and the University of Alabama at Birmingham Cancer Data Analysis portal were also utilized. Some essential results were further verified using in vitro experiments using HepG2 liver cancer cells. A signature consisting of three genes associated with the progression and prognosis of HCC and FA metabolism was identified. When samples were scored based on the expression of these genes and divided according to the median value, the higher score group showed a worse outcome and repressive immune microenvironment than the lower score group. Downstream pathways such as hypoxia, IL6/JAK/STAT3 and epithelial-mesenchymal transition were found to be significantly activated in the higher score group. As the core factor in the signature, mitochondrial ribosomal protein L35 (MRPL35) was found to be upregulated in HCC and to have certain impacts on the dysregulation of effective immunity. Further investigations and in vitro experiments indicated that MRPL35 facilitates the migration and invasion abilities of liver cancer, and the resistance of HCC to treatment. These findings have important implications regarding the characteristics and mechanisms of metastasis in liver cancer, and provide a promising signature based on FA metabolism-related genes that may be used to predict outcomes and explored as a novel therapeutic target in liver cancer.

Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice.

Metastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (KrasG12D/+;Alb-Cre), p53 haploinsufficiency (p53+/-) or Tsc1 loss (Tsc1fl/fl;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.

KNTC1 knockdown inhibits proliferation and metastases of liver cancer.

To investigate the mechanism of kinetochore-associated protein 1 (KNTC1) in hepatocellular carcinoma. To query the TCGA database for KNTC1 expression in hepatocellular carcinoma. Detection of protein and mRNA levels of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449. Cell proliferation, migration and invasion ability were examined after KNTC1 knockdown in SK-Hep-1 and Huh7. Proteins related to KNTC1 were identified through protein interregulation, and their role in hepatocellular carcinoma was investigated. Our results showed that KNTC1 was significantly upregulated in hepatocellular carcinoma tissues and was associated with poorer prognostic survival. The expression of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449 was significantly higher than that in normal hepatocyte line L02. Knockdown of KNTC1 in SK-Hep-1 and Huh7 significantly inhibited cell viability, migration ability and invasion ability. KNTC1 is involved in the regulation of hepatocellular carcinoma through its interaction with cyclin-dependent kinase 1 (CDK1). Knockdown of KNTC1 inhibited CDK1 expression, while CDK1 overexpression was able to rescue the regulation of KNTC1 on the viability, migration and invasive ability of hepatocellular carcinoma cell lines. Knockdown of KNTC1 was found to resulted a cell cycle arrest at the S-phase, potentially through the modulation of CDK1, leading to decreased migration and invasion of hepatocellular carcinoma cells. Moreover, knockdown of KNTC1 in mouse transplanted tumors significantly inhibits tumor growth. Inhibition of high expression of KNTC1 in hepatocellular carcinoma was effective in suppressing the progression of hepatocellular carcinoma cells after knockdown. It may be a potential target for the treatment of hepatocellular carcinoma.

FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation

FBXO28 is a member of F-box proteins that are the substrate receptors of SCF (SKP1, CULLIN1, F-box protein) ubiquitin ligase complexes. Despite the implications of its role in cancer, the function of FBXO28 in epithelial-mesenchymal transition (EMT) process and metastasis for cancer remains largely unknown. Here, we report that FBXO28 is a critical negative regulator of migration, invasion and metastasis in human hepatocellular carcinoma (HCC) in vitro and in vivo. FBXO28 expression is upregulated in human epithelial cancer cell lines relative to mesenchymal counterparts. Mechanistically, by directly binding to SNAI2, FBXO28 functions as an E3 ubiquitin ligase that targets the substrate for degradation via ubiquitin proteasome system. Importantly, we establish a cooperative function for PKA in FBXO28-mediated SNAI2 degradation. In clinical HCC specimens, FBXO28 protein levels positively whereas negatively correlate with PKAα and SNAI2 levels, respectively. Low FBXO28 or PRKACA expression is associated with poor prognosis of HCC patients. Together, these findings elucidate the novel function of FBXO28 as a critical inhibitor of EMT and metastasis in cancer and provide a mechanistic rationale for its candidacy as a new prognostic marker and/or therapeutic target in human aggressive HCC.

Friend or foe? The elusive role of hepatic stellate cells in liver cancer.

Liver fibrosis is a substantial risk factor for the development and progression of liver cancer, which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Studies utilizing cell fate mapping and single-cell transcriptomics techniques have identified quiescent perisinusoidal hepatic stellate cells (HSCs) as the primary source of activated collagen-producing HSCs and liver cancer-associated fibroblasts (CAFs) in HCCand liver metastasis, complemented in iCCA by contributions from portal fibroblasts. At the same time, integrative computational analysis of single-cell, single-nucleus and spatial RNA sequencing data have revealed marked heterogeneity among HSCs and CAFs, with distinct subpopulations displaying unique gene expression signatures and functions. Some of these subpopulations have divergent roles in promoting or inhibiting liver fibrogenesis and carcinogenesis. In this Review, we discuss the dual roles of HSC subpopulations in liver fibrogenesis and their contribution to liver cancer promotion, progression and metastasis. We review the transcriptomic and functional similarities between HSC and CAF subpopulations, highlighting the pathways that either promote or prevent fibrosis and cancer, and the immunological landscape from which these pathways emerge. Insights from ongoing studies will yield novel strategies for developing biomarkers, assessing prognosis and generating new therapies for both HCC and iCCA prevention and treatment.

Morphometric characterization and temporal temperature measurements during hepatic microwave ablation in swine.

Heat-induced destruction of cancer cells via microwave ablation (MWA) is emerging as a viable treatment of primary and metastatic liver cancer. Prediction of the impacted zone where cell death occurs, especially in the presence of vasculature, is challenging but may be achieved via biophysical modeling. To advance and characterize thermal MWA for focal cancer treatment, an in vivo method and experimental dataset were created for assessment of biophysical models designed to dynamically predict ablation zone parameters, given the delivery device, power, location, and proximity to vessels. MWA zone size, shape, and temperature were characterized and monitored in the absence of perfusion in ex vivo liver and a tissue-mimicking thermochromic phantom (TMTCP) at two power settings. Temperature was monitored over time using implanted thermocouples with their locations defined by CT. TMTCPs were used to identify the location of the ablation zone relative to the probe. In 6 swine, contrast-enhanced CTs were additionally acquired to visualize vasculature and absence of perfusion along with corresponding post-mortem gross pathology. Bench studies demonstrated average ablation zone sizes of 4.13±1.56cm2 and 8.51±3.92cm2, solidity of 0.96±0.06 and 0.99±0.01, ablations centered 3.75cm and 3.5cm proximal to the probe tip, and temperatures of 50 ºC at 14.5±13.4s and 2.5±2.1s for 40W and 90W ablations, respectively. In vivo imaging showed average volumes of 9.8±4.8cm3 and 33.2±28.4cm3 and 3D solidity of 0.87±0.02 and 0.75±0.15, and gross pathology showed a hemorrhagic halo area of 3.1±1.2cm2 and 9.1±3.0cm2 for 40W and 90W ablations, respectfully. Temperatures reached 50ºC at 19.5±9.2s and 13.0±8.3s for 40W and 90W ablations, respectively. MWA results are challenging to predict and are more variable than manufacturer-provided and bench predictions due to vascular stasis, heat-induced tissue changes, and probe operating conditions. Accurate prediction of MWA zones and temperature in vivo requires comprehensive thermal validation sets.

Managing intractable pain with neuraxial infusion at home.

A case study of a 9-year-old child with complex pain secondary to metastatic liver cancer, who eventually required intrathecal drug delivery (ITDD) of analgesia. Multi-modal symptom control strategies were deployed to achieve the child's and parental wishes for end-of-life care (EoLC) at home using ITDD. The following recommendations are made for nursing practice in paediatric palliative care (PPC); rigorous risk assessment, exemplary communication with the identification of a coordinating team, timely training needs assessment and the delivery of training from hospital based experts in ITDD practice, comprehensive symptom management plan and 24/7 access to specialist palliative care teams were essential for safe nursing practice. In this case, robust risk assessment and mitigations enabled challenges to be safely addressed with a successful outcome, extending the boundaries of PPC home care.

Application of respiratory sensing technique in CT-guided radiofrequency ablation of liver malignancies.

This study aimed to examine the effectiveness and safety of respiratory sensing methods in nonvascular interventional therapy of liver tumors. In this study, 64 patients with primary liver cancer or liver metastasis were retrospectively analyzed. According to two widely used clinical techniques to limit respiratory movement-breath holding and respiratory sensing technology-they were randomly allocated into two groups: respiratory gated and respiratory training. We aimed to compare the application and effect of these two techniques in the nonvascular interventional therapy of liver tumors. The puncture times of the respiratory-gated and respiratory training groups were 5.34 ± 2.47 and 8.41 ± 3.63 min, respectively. Puncture errors were 10.00 ± 2.65 and 12.81 ± 8.57 mm, respectively. Puncture adjustment times were 3.06 ± 1.26 and 4.87 ± 1.69 times, respectively, and the differences were statistically significant (P < 0.01). Respiratory sensing technology has been effectively used to assist in puncturing liver malignant tumors using a radiofrequency (RF) ablation (RFA) system that is guided by computed tomography (CT) scans. It is superior to the classical breath-holding step puncture technique in terms of puncture time, puncture error, and puncture needle adjustment times.

ETV4 facilitates proliferation, migration, and invasion of liver cancer by mediating TGF-β signal transduction through activation of B3GNT3.

Metastasis of liver cancer (LC) is the main cause of its high mortality. ETV4 is a critical regulatory factor in promoting LC progression, but the mechanism that ETV4 impacts LC proliferation, migration, and invasion is poorly understood. Investigation of the molecular mechanism of LC metastasis is conducive to developing effective drugs that prevent LC metastasis. Expression of ETV4 and its target gene B3GNT3 in LC tissue was analyzed by bioinformatics, and the result was further verified in LC cells by qRT-PCR. In vitro cellular assays evaluated the impact of ETV4 on the proliferation, migration, and invasion of LC cells. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assay were conducted to analyze the interaction between B3GNT3 and ETV4. SB525334 suppressor was used to treat and access the activation of ETV4 on the TGF-β pathway. We discovered that ETV4 and B3GNT3 were evidently up-regulated in LC, and high expression of ETV4 was coupled to the increase of proliferation, migration, and invasion of LC cells and epithelial-mesenchymal transition ability. Besides, ETV4 could bind to the B3GNT3 promoter and activate its transcription. Knockdown of B3GNT3 could prominently suppress the effect of up-regulated ETV4 on LC cells. Meanwhile, ETV4 could activate the TGF-β signaling pathway via B3GNT3, while SB525334 treatment notably repressed the functions of ETV4. ETV4 emerges as a driven oncogene in LC, and the ETV4/B3GNT3-TGF-β pathway promotes proliferation, migration, invasion, and epithelial-mesenchymal transition progress of LC. Inhibition of the pathway may provide an underlying method for the prevention and treatment of LC metastasis.

Factors influencing the selection of liver resection for adult patients with colorectal cancer liver metastases

The selection of liver resection surgery for adult patients with colorectal cancer liver metastases is a complex process influenced by various patient, tumor, and surgical factors. A systematic review was conducted with the PICO model research question, "are hepatectomy surgeries more effective than non-surgical treatment or alternative surgical treatments in improving survival and quality of life in adult patients?". A comprehensive scientific literature search was conducted using recognized medical and scientific databases. A narrative-question-answer synthesis was used to provide a comprehensive overview of the factors influencing the choice of hepatic recession surgery in adult patients with liver metastatic liver cancer. Concluding, the choice of liver surgery in adults with liver cancer metastasis depends on a wide range of factors such as the patient's age, characteristics of the tumor, peri and postoperative complications, and the number of metastases. Considering this is essential to the decision-making process and should be individualized for each patient.

Post-therapeutic microRNA-146a in liquid biopsies may determine prognosis in metastatic gastrointestinal cancer patients receiving 90Y-radioembolization

PurposeThe role of microRNA-146a (miR-146a) in defining the tumor immune microenvironment (TIME) is well established. The aim of this study was to evaluate circulating miR-146a as an early prognostic marker of 90Y-radioembolization (90Y-RE) in metastatic liver cancer and to assess the correlation between circulating miR-146a and TIME cellular composition in distant, yet untreated metastases.MethodsTwenty-one patients with bilobar liver lesions from gastro-intestinal cancer underwent lobar 90Y-RE. Biopsy of contralateral lobe abscopal tumors was acquired at the onset of a second treatment session at a median of 21 days after initial RE, immediately prior to ablation therapy of the contralateral lobe tumor. miR-146a was measured by RT-qPCR in plasma collected 24 h before (T1) and 48 h after (T2) initial unilobar 90Y-RE. The level of miR-146a was correlated with the infiltration of CD4 + , CD8 + , FoxP3 T cells, CD163 + M2 macrophages and immune-exhausted T cells in the abscopal tumor tissue acquired before the second treatment session.ResultsPlasma samples collected at T2 showed a higher concentration of miR-146a with respect to T1 in 43% of the patients (p = 0.002). In these patients, tumors revealed a pro-tumorigenic immune composition with enrichment of Tim3 + immune exhausted cells (p = 0.021), in combination with a higher infiltration of CD163 + M2 macrophages and a lower infiltration of CD8 + T cells. Patients with a higher level of miR-146a after 90Y-RE showed a trend to shorter OS (p = 0.055).ConclusionmiR-146a may represent a novel prognostic biomarker for 90Y-radioembolization in metastatic liver cancer.