Liver Metastases Research Articles

Liver Resection With Extrahepatic Disease: A Population-Based Analysis of Thoughtful Selection.

The oncologic benefit of liver resection for colorectal liver metastases (CRLM) in the setting of concurrent extrahepatic disease (EHD) is controversial. We performed a population-based, cross-sectional study to determine the practice patterns and overall survival (OS) of patients with CRLM + EHD who underwent liver resection. Patients with CRLM + EHD were identified using the California Cancer Registry from 2000 to 2019. Records were linked to the Office of Statewide Health Planning Inpatient Database. Patient demographics, clinical characteristics, and survival were compared between CRLM + EHD patients with and without liver resection. Of 170 978 patients with CRLM, 62 003 (36%) had concurrent EHD (CRLM + EHD). In all, 3736 (6%) of CRLM + EHD underwent liver resection compared to 22% of patients with liver limited CRLM. Compared to CRLM + EHD without liver resection, CRLM + EHD with resection were younger, had fewer comorbidities, received higher frequencies of perioperative chemotherapy, and were more likely to have only a single site of EHD rather than multiple sites. Median OS was significantly higher for CRLM + EHD with resection compared to without (52 vs. 27 months, HR 0.46 [95% CI 0.44-0.47], p < 0.001). Regarding the location of EHD, this survival benefit was observed with liver resection for lung, peritoneal, intraabdominal lymph nodes, ovarian, and bone metastases. In a large population-based setting, subsets of CRLM + EHD patients that undergo liver resection are associated with prolonged survival. These results support surgery with thoughtful patient selection to optimize survival outcomes in this population.

HEPATECTOMIA CONVENCIONAL EM DOIS ESTÁGIOS VERSUS ALPPS: UMA REVISÃO DE LITERATURA SOBRE O TRATAMENTO DE METÁSTASE HEPÁTICA COLORRETAL

This study compared the outcomes of two modalities of hepatectomies for the treatment of colorectal liver metastasis. The research is justified by the high morbidity and mortality associated with hepatic surgical interventions, as these require a delicate approach and intricate techniques, posing a challenge in the surgical field. The aim was to highlight the operative technique with greater efficacy, outlining its associated benefits and risks, in order to identify the definitively superior aspects within the literature among the analyzed modalities. The methodology involved a literature review of 46 articles, written in Portuguese and English, available in various databases from 2019 to 2024. The results indicated that ALPPS had limited advantages compared to HDE, demonstrating greater surgical efficacy, while the rates of perioperative complications and short-term outcomes were comparable between the two techniques, with no evidence of differences in reducing morbidity and mortality. Conversely, there were discrepancies in determining the overall survival rates between the two techniques, underscoring the need for further studies on the topic and the exploration of less invasive methods with lower rates of surgical morbidity and mortality.

Clinical Outcomes and Prognostic Factors for R0 Resected Colorectal Cancer with Synchronous Peritoneal Metastasis: A Retrospective Study.

Peritoneal metastasis indicates a poor prognosis in patients with colorectal cancer (CRC). Studies have shown improved prognosis in patients after removal of peritoneal dissemination, and this surgery is recommended if not excessively invasive. The aim of this study was to examine clinical outcomes and prognostic factors for R0 resected CRC with synchronous peritoneal metastasis. We analyzed data retrospectively from 250 patients with stage IV CRC who underwent R0 resection at our hospital. The patients were divided into three groups according to the type of surgery: non-resected (N), palliative primary tumor resection (P), and R0 resection (R0) groups. Overall survival (OS) and recurrence-free survival (RFS) were investigated and clinicopathological parameters were analyzed for prognostic significance. The 3-year OS was 57.2% in the R0 group. The R0 group had a significantly higher 3-year OS than that in the other groups (p < 0.0001). Multivariate analysis revealed that histological type, lymphatic and venous invasion, liver metastasis, R0 resection, and perioperative chemotherapy were independent prognostic factors. The 5-year RFS in the R0 group was 26.5%. Multivariate analysis revealed that the number of peritoneal metastases and surgical procedure were independent prognostic factors. Laparoscopic surgery had better 5-year RFS in the R0 group compared with that in the open surgery group (p = 0.0044). R0 resection of colorectal cancer with synchronous peritoneal metastasis should be considered for improving long-term survival. The laparoscopic approach for this disease is another promising method to prolong survival in patients with R0 resection.

A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer

The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3’ UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.

Prognostic Factors for Patients with Small-Cell Lung Cancer Treated with Chemoimmunotherapy: A Retrospective Multicenter Study

Background: This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Methods: Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an OS of 6–24 months, and poor corresponded to an OS &lt; 6 months. Multivariate Cox regression analyses were used to evaluate prognostic factors. Results: Of 130 patients, the proportions of performance status decline and liver metastasis were significantly higher in the poor-prognosis group. With regard to the laboratory findings, neutrophil/lymphocyte ratios and albumin levels differed significantly among the groups. Multivariate analysis showed that the independent prognostic factors for OS were liver metastasis and decreased albumin levels (&lt;3.5 mg/dL). After classifying the patients into three groups according to the quantities of these prognostic factors, the OS differed significantly among the groups (18.3 vs. 13.5 vs. 3.8 months; p &lt; 0.001). The incidence of immune-related adverse events (irAEs) was higher in patients without these prognostic factors than in those with both (36% vs. 5%; p = 0.01). Conclusion: Liver metastasis and decreased albumin levels are independent unfavorable prognostic factors. Patients with both prognostic factors showed unfavorable OS; however, patients without these factors may have a favorable prognosis but be at greater risk of irAEs.

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is often resistant to therapy. An immune suppressive tumor microenvironment (TME) and oncogenic mutations in KRAS have both been implicated as drivers of resistance to therapy. Mitogen-activated protein kinase (MAPK) inhibition has not yet shown clinical efficacy, likely because of rapid acquisition of tumor-intrinsic resistance. However, the unique PDAC TME may also be a driver of resistance. We found that long-term focal adhesion kinase (FAK) inhibitor treatment led to hyperactivation of the RAS/MAPK pathway in PDAC cells in mouse models and tissues from patients with PDAC. Concomitant inhibition of both FAK (with VS-4718) and rapidly accelerated fibrosarcoma and MAPK kinase (RAF-MEK) (with avutometinib) induced tumor growth inhibition and increased survival across multiple PDAC mouse models. In the TME, cancer-associated fibroblasts (CAFs) impaired the down-regulation of MYC by RAF-MEK inhibition in PDAC cells, resulting in resistance. By contrast, FAK inhibition reprogramed CAFs to suppress the production of FGF1, which can drive resistance to RAF-MEK inhibition. The addition of chemotherapy to combined FAK and RAF-MEK inhibition led to tumor regression, a decrease in liver metastasis, and improved survival in KRAS-driven PDAC mouse models. Combination of FAK and RAF-MEK inhibition alone improved antitumor immunity and priming of T cell responses in response to chemotherapy. These findings provided the rationale for an ongoing clinical trial evaluating the efficacy of avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in patients with PDAC and may suggest further paths for combined stromal and tumor-targeting therapies.

In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease.

A deeper understanding of colorectal cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p-value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.

ASO Author Reflections: Biological Contraindications to Surgery in Colorectal Liver Metastasis.

ASO Author Reflections: Biological Contraindications to Surgery in Colorectal Liver Metastasis.

Role of Immunotherapy in Gastroesophageal Cancer with Liver Metastasis.

The role of immune checkpoint inhibitors (ICIs) for patients with gastroesophageal (GE) cancer with liver metastasis remains unclear. Our objective was to investigate if ICIs are beneficial in patients with GE cancer with liver metastasis. We searched PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase III randomized clinical trials (RCTs) testing ICIs in metastatic/advanced GE cancer from 2017 to 2023. Seven studies were included. OS was similar among all patients (HR 0.72 [0.67,0.77], p < .001), in patients without (HR 0.73 [0.67,0.81], p < .001, I2 = 0.0%), and with liver metastasis (HR 0.74 [0.67,0.81], p < .001, I2 = 0.0%). PFS was also similar among all patients (HR 0.63 [0.57,0.70], p < .001), without (HR 0.62 [0.51,0.76], p < .001), and with liver metastasis (HR 0.66 [0.57,0.76], p < .001). ICIs showed no difference in benefit in patients with GE cancer regardless of liver metastasis. Future studies could focus on deciphering the tumor microenvironment of liver metastasis as an area of translational research.

Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence

Background/Objectives: Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients. Methods: The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence. Results: LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age. Conclusions: Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes.

Clinical impact of TP53 functional mutations in patients with metastatic colorectal cancer treated with bevacizumab and chemotherapy.

Clinical and experimental studies indicate that the tumor protein p53 (TP53) gene loss of function due to missense mutations (MMs) may confer sensitivity to anti-angiogenics. This effect seems to be linked to cross-talk mechanisms among TP53, vascular endothelial growth factor (VEGF), and VEGF receptors. We investigated whether specific TP53 MMs are associated with clinical outcomes of patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus Bevacizumab. The study focused on KRAS-mutated, liver-only mCRC cases as a homogeneous subgroup that may represent a relevant setting for exploring this association. MMs were identified on primary tumors. MMs were classified by mutant-specific residual transcriptional activity scores (TP53RTAS) as transcriptionally inactive (TP53inactive = TP53RTAS 0%) or active (TP53active = TP53RTAS ≥ 1%) and used for stratifying patients in progression-free survival (PFS), response rate, and overall survival (OS) analyses. The study population consisted of 62 patients. MMs were found in 39 cases (62%) with 16 having TP53inactive and 23 TP53active MMs. Patients with TP53inactive MMs showed better PFS in comparison with the remaining groups (wild-type and TP53active). This effect was retained in the multivariate model. A similar clinical impact was observed in the OS analysis. There was a significant difference in the overall response rate and rate of post-treatment resection of liver metastases between the TP53inactive and the wild-type or TP53active MMs cases. Specific TP53 MMs may identify sub-groups of patients who benefit from Bevacizumab-based systemic therapy and these findings could lead to novel tailored treatment strategies in this setting.

The role of exosomes in liver cancer: comprehensive insights from biological function to therapeutic applications.

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.

Hepatic Encephalopathy Without Hyperammonemia in the Setting of Liver Metastases by a Pancreatic Neuroendocrine Tumor

Hepatic Encephalopathy Without Hyperammonemia in the Setting of Liver Metastases by a Pancreatic Neuroendocrine Tumor

Comparative analysis of clinical treatment outcomes: Breath-hold vs. free-breathing techniques in liver stereotactic body radiotherapy.

The aim of this study was to clarify the safety and efficacy of breath-hold irradiation in liver stereotactic body radiotherapy (SBRT). A retrospective analysis was conducted on 57 consecutive patients who received SBRT for hepatocellular carcinoma or liver metastases between 2013 and 2021. Breath-hold irradiation was implemented for patients treated after April 2020. The median follow-up period for all patients was 16.4 months (IQR: 7.36-20.9). The 2-year overall survival rate was 64.4% (95% CI: 47.4-77.2), and the local control rate was 84.3% (95% CI: 69.7-92.3) for all patients. The 1-year overall survival was 80.0% (95% CI: 60.8-90.5) versus 82.0% (95% CI: 53.5-93.9) in the free-respiratory (FR) group versus the breath-hold (BH) group, respectively (P = 0.60). The 1-year local control rates were 78.1% (95% CI: 57.5-89.5) in the FR group and 95.7% (95% CI: 72.9-99.4) in the BH group, respectively (P = 0.16). Radiation-induced liver injury, defined by an escalation of ≥2 in Child-Pugh score, was observed in four patients within each group (FR 13% vs. BH 15%). There were no gastrointestinal adverse events of Grade 3 or higher. Breath-hold irradiation can be safely administered and has demonstrated clinical potential in improving local control. Further research into dose escalation using breath-hold techniques is warranted.

Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival

ObjectivePotential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. MethodsPatients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. ResultsSeventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), P = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), P = 0.031). ConclusionR0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).

Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer.

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, primarily due to liver metastasis. This study explores the role of centromere protein N (CENP-N) in mediating the methylation of septin 9 (SEPT9) and its subsequent effects on aerobic glycolysis and liver metastasis in CRC. We employed in vitro and in vivo experiments, including single-cell RNA sequencing, methylation-specific PCR (MSP), ChIP assays, and various functional assays to assess the impact of CENP-N and SEPT9 on CRC cell proliferation, migration, invasion, and metabolic reprogramming. Our data reveal that CENP-N directly interacts with SEPT9, enhancing its methylation at specific lysine residues. This modification significantly upregulates key glycolytic enzymes, thereby promoting aerobic glycolysis, CRC cell proliferation, and migration. In vivo studies further demonstrate that the CENP-N/SEPT9 axis facilitates liver metastasis of CRC, as confirmed by fluorescence imaging and histological analysis. This study identifies a novel pathway where CENP-N-mediated methylation of SEPT9 drives metabolic reprogramming and metastasis in CRC. These findings suggest potential therapeutic targets for inhibiting CRC progression and liver metastasis, offering new insights into CRC pathogenesis.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis.

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5cm or up to 3 tumors smaller than 3cm and tumors 1cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4months (interquartile range [IQR] 29.9-46.7) versus 120.5months (IQR 97.2-134.0), respectively (p<0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.

Uveal melanoma (UM), the predominant primary ocular malignancy, often progresses to liver metastasis with limited therapeutic options. The interplay of the tumor microenvironment, encompassing secreted soluble factors, plays a crucial role in facilitating liver metastasis. In this study, the role is elucidated of the neural growth factor-inducible gene (VGF), a secreted neuropeptide precursor, in Gαq mutant UM. Employing a multiomics approach, encompassing transcriptomic and secretomic analyses, the intricate involvement of VGF in UM progression is unveiled. VGF is upregulated in Gαq mutant UM cells and associated with poor prognosis of UM patients. Targeting VGF significantly suppressed the growth of UM in vitro and in vivo. Further evidence shows that VGF is regulated by Gαq through MAPK/CREB pathway. Mechanistically, CREB modulates VGF expression by directly binding to consensus DNA response elements in the promoters of the VGF gene. Combined inhibition of Gαq and MEK remarkably reduces tumor burden in the UM xenograft model. Notably, VGF triggers liver metastatic colonization of UM and activates the fibrosis of hepatic stellate cells (HSCs), creating a favorable microenvironment, through an autocrine and paracrine loop. Furthermore, VGF directly binds to TGFBR2 and regulates TGF-β-SMAD signaling pathway, thereby regulating genes associated with endothelial-mesenchymal transition (EMT) to promote metastasis. Taken together, these findings identify VGF as a pivotal driver in the progression and metastasis of Gαq mutant UM and confers a promising therapeutic target and strategy for UM patients.

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.