Mechanistic insights into xanthomicrol as the active anti-HCC ingredient of Phytolacca acinosa Roxb.: A network pharmacology analysis and transcriptomics integrated experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. AIM OF THE STUDY: The research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Employing network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. RESULTS: Network pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. CONCLUSIONS: Xanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.

Case report: Massive hepatocellular carcinoma with complete response to the non-surgical systematic treatment strategy.

Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) remains as high as 70%. A complete clinical response has not been observed without surgical resection. Here, we report a rare case of clinical complete response and long-term survival in a patient with massive HCC receiving treatment with immunotherapy, anti-angiogenic therapy, and radiotherapy. Case description: A 38-year-old woman presented to our hospital for abdominal pain that persisted for 3 months. She was diagnosed as Barcelona Clinic Liver Cancer(BCLC) stage A, with a Cancer of the Liver Italian Program (CLIP) score of 3, American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging systems stage IB. She refused surgical resection and trans-arterial chemoembolization and accepted a non-invasive systematic treatment strategy involving immunotherapy, anti-angiogenic therapy, and radiotherapy. Her tumor burden decreased, and she experienced partial response before radiotherapy. Following radiotherapy, she experienced a complete clinical response and has been alive for more than 36 months after her initial presentation. She is currently alive. Conclusion: A non-invasive systematic treatment strategy is a potential radical treatment option for patients with massive HCC.

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis.

BACKGROUND: MET and AXL dysregulations are implicated in acquired resistance to EGFR-TKIs in NSCLC. But consensus on the optimal definition for MET/AXL dysregulations in EGFR-mutant NSCLC is lacking. Here, we investigated the efficacy and tolerability of ningetinib (a MET/AXL inhibitor) plus gefitinib in EGFR-mutant NSCLC, and evaluated the clinical relevance of MET/AXL dysregulations by different definitions. METHODS: Patients in this phase 1b dose-escalation/dose-expansion trial received ningetinib 30 mg/40 mg/60 mg plus gefitinib 250 mg once daily. Primary endpoints were tolerability (dose-escalation) and objective response rate (dose-expansion). MET/AXL status were analyzed using FISH and IHC. RESULTS: Between March 2017 and January 2021, 108 patients were enrolled. The proportion of MET focal amplification, MET polysomy, MET overexpression, AXL amplification and AXL overexpression is 18.1 %, 5.6 %, 55.8 %, 8.1 % and 45.3 %, respectively. 6.8 % patients have concurrent MET amplification and AXL overexpression. ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade. CONCLUSIONS: This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20160875.

Climate and mineral accretion as drivers of mineral-associated and particulate organic matter accumulation in tidal wetland soils.

Tidal wetlands sequester vast amounts of organic carbon (OC) and enhance soil accretion. The conservation and restoration of these ecosystems is becoming increasingly geared toward "blue" carbon sequestration while obtaining additional benefits, such as buffering sea-level rise and enhancing biodiversity. However, the assessments of blue carbon sequestration focus primarily on bulk SOC inventories and often neglect OC fractions and their drivers; this limits our understanding of the mechanisms controlling OC storage and opportunities to enhance blue carbon sinks. Here, we determined mineral-associated and particulate organic matter (MAOM and POM, respectively) in 99 surface soils and 40 soil cores collected from Chinese mangrove and saltmarsh habitats across a broad range of climates and accretion rates and showed how previously unrecognized mechanisms of climate and mineral accretion regulated MAOM and POM accumulation in tidal wetlands. MAOM concentrations (8.0 ± 5.7 g C kg-1 ) (±standard deviation) were significantly higher than POM concentrations (4.2 ± 5.7 g C kg-1 ) across the different soil depths and habitats. MAOM contributed over 51.6 ± 24.9% and 78.9 ± 19.0% to OC in mangrove and saltmarsh soils, respectively; both exhibited lower autochthonous contributions but higher contributions from terrestrial or marine sources than POM, which was derived primarily from autochthonous sources. Increased input of plant-derived organic matter along the increased temperature and precipitation gradients significantly enriched the POM concentrations. In contrast, the MAOM concentrations depended on climate, which controlled the mineral reactivity and mineral-OC interactions, and on regional sedimentary processes that could redistribute the reactive minerals. Mineral accretion diluted the POM concentrations and potentially enhanced the MAOM concentrations depending on mineral composition and whether the mineral accretion benefited plant productivity. Therefore, management strategies should comprehensively consider regional climate while regulating sediment supply and mineral abundance with engineering solutions to tap the OC sink potential of tidal wetlands.

Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer.

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45- nonimmune cells and 196,473 CD45+ immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. F3+ fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, MCAM+ fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.

Electrical Pulse Induced One-step Formation of Atomically Dispersed Pt on Oxide Clusters for Ultra-Low-Temperature Zinc-Air Battery.

Atomically dispersed sites anchored on small oxide clusters are attractive new catalytic materials. Herein, we demonstrate an electrical pulse approach to synthesize atomically dispersed Pt on various oxide clusters in one step with nitrogen-doped carbon as the support (Pt1 -MOx /CN). As a proof-of-concept application, Pt1 -FeOx /CN is shown to exhibit high activity for oxygen reduction reaction (ORR) with a half-wave potential of 0.94 V vs RHE, in contrast to the poor catalytic performance of atomically dispersed Pt on large Fe2 O3 nanoparticles. Our work has revealed that, by tuning the size of the iron oxide down to the cluster regime, an optimal OH* adsorption strength for ORR is achieved on Pt1 -FeOx /CN due to the regulation of Pt-O bonds. The unique structure and high catalytic performance of Pt1 -FeOx /CN enable the Zinc-Air batteries an excellent performance at ultralow temperature of -40 °C with a high peak power density of 45.1 mW cm-2 and remarkable cycling stability up to 120 h.

N6-Methyladenosine (m6A)-Related lncRNAs Are Potential Signatures for Predicting Prognosis and Immune Response in Lung Squamous Cell Carcinoma.

Background: Despite increasing understanding of m6A-related lncRNAs in lung cancer, the role of m6A-related lncRNAs in the prognosis and treatment of lung squamous cell carcinoma is poorly understood to date. Thus, the current study aims to elucidate its role and build a model to predict the prognosis of LUSC patients. Materials and Methods: The data of the current study were accessed from the TCGA database. Pearson correlation analysis was performed to identify lncRNAs correlated to m6A. Next, an m6A-related lncRNAs risk model was built using a single factor, least absolute association, selection operator, and multivariate Cox regression analysis. Results: The relevance between 23 m6A genes and 14,056 lncRNAs is shown by Pearson correlation analysis by Sankey diagram. Multivariate Cox regression analysis determined that 11 m6A-lncRNAs show predictive potential in prognosis, which is confirmed by the consistency index, Kaplan-Meier analysis, principal component analysis, and ROC curve. Additionally, the immune analysis showed that the enrichment of immune cells, major histocompatibility complex molecules, and immune checkpoints in the high and low-risk subgroups were markedly disparate, with the high-risk group showing a stronger immune escape ability and a worse response to immunotherapy. Conclusion: In conclusion, the risk model based on m6A-related lncRNAs showed great promise in predicting the prognosis and the efficacy of immunotherapy.

Notch signaling mutations increase intra-tumor chemokine expression and predict response to immunotherapy in colorectal cancer.

BACKGROUND: The Notch signaling mutation is associated with enhanced anti-tumor immune response in colorectal cancer (CRC). In this study, we aim to investigate the underlying mechanism and the predictive potential of Notch signaling mutation for responding to immunotherapy in CRC. METHODS: We analyzed the immune response associated genes in CRC with Notch signaling mutation concomitant with or without microsatellite instability (MSI) using TCGA dataset and investigated the mutation profiles of the Notch signaling pathway using cBioPortal. The Notch signaling scores and immune cell infiltration scores in different groups were calculated. We applied the Kaplan-Meier method for survival analysis in CRC patients who underwent immunotherapy, and the log-rank test to determine the statistically significant differences in survival. Notch1-knock-down cell line was constructed to detect the pathway and gene variations. RESULTS: We found that Notch signaling pathway mutation was associated with activated immune response, especially in those with MSI. Such association is useful for predicting a prolonged overall survival of CRC patients who underwent immune checkpoint inhibitor treatment. The mutation resulted in the functional loss of Notch signaling and may modulate the tumor immune microenvironment by increasing the expression of chemokines that are important for recruiting immune cells. CONCLUSIONS: The Notch signaling mutation can modulate the chemotaxis of immune cells by upregulating the chemokine levels of the tumor immune microenvironment, and CRC patients with Notch signaling pathway mutation have better overall survival after immune checkpoint inhibitor treatment.

Survival Improvement in Patients with Renal Cell Carcinoma and Disparities between Different Sexes, Races, and Socioeconomic Status: 1977-2016.

Objective: Rare research of renal cell carcinoma (RCC) has been made in a comprehensive and full description based on a long period of time as yet. This study was aimed at investigating the incidence and relative survival rates (RSRs) of RCC in the past forty years and to disclose the impact of sex, race, and socioeconomic status (SES) on RCC. Methods: The data as variables, including age, gender, race, and SES, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. SES was divided into three levels: low poverty, medium poverty, and high poverty. The medium- and high-poverty groups were integrated into one group in all analyses. The RSRs were calculated using period analysis methodology. Summary statistics including incidence and RSRs were analyzed by Kaplan-Meier and Cox proportional hazards models with GraphPad Prism 8.0.1 software and Stata 12.0 software. Results: A total of 77,513 patients diagnosed with RCC were enrolled in this study, showing an increased incidence and 10-year RSRs from 1977 to 2016. Patients older than 60 years had the highest incidence and the lowest RSRs. This research also showed significant disparities between different groups: incidence in males, blacks, and medium-high poverty groups was higher than that in females, whites, and low poverty groups, while RSRs were lower. For sex groups, the disparity of RSRs was obvious among patients who were 30-59 years old, but not among those younger than 29 years or older than 60 years. Based on SES, the survival gaps between different SES groups were getting wider over the past forty years. Conclusion: This study showed how age, sex, race, and SES affected the incidence and RSRs of RCC, which may be beneficial for both better designed clinical trials and efficient prevention methods.

Regulating Sn self-doping and boosting solar water splitting performance of hematite nanorod arrays grown on fluorine-doped tin oxide via low-level Hf doping.

Hematite (α-Fe2O3) nanorod arrays grown on fluorine-doped tin oxide (FTO) substrate exhibit outstanding solar water splitting efficiency, benefiting from Sn self-doping induced by high-temperature annealing. However, this Sn self-doping couldn't be freely controlled without changing the optimized annealing conditions, which limits the further improvement of their photoelectrochemical (PEC) properties. Here, we report a facile hydrothermal synthesis with subsequent annealing approach to regulate the Sn diffusion via hafnium (Hf) doping as well as enhance the PEC performance of hematite photoanode. Upon increasing the Hf doping concentration, the Sn self-doping content was continuously suppressed. The very low doping-level of Hf (i.e., atomic Hf/Fe = 0.13 âˆ¼ 1.54%) was sufficient for enhancing the electrical conductivity. The Hf-doped α-Fe2O3 with the optimized dopant concentration (Hf/Fe = 1.34%, denoted as 0.25-Hf-Fe2O3) showed a photocurrent density of 1.79 mA/cm2 at 1.23 V vs. RHE, 70% higher than that of the Sn self-doped one (Pristine-Fe2O3). The donor density of 0.25-Hf-Fe2O3 increased 2.5 times compared to Pristine-Fe2O3 while its space-charge resistance and charge transfer resistance declined by 40% and 22%, respectively, verifying Hf doping improves the charge carrier density and accelerates the charge transfer for solar water oxidation. We offered here a prospective dopant alternative for preparing superior hematite-based photoanode.

Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers.

The striatin-interacting phosphatase and kinase (STRIPAK) complexes integrate extracellular stimuli that result in intracellular activities. Previously, we discovered that STRIPAK is a key machinery responsible for loss of the Hippo tumor suppressor signal in cancer. Here, we identified the Hippo-STRIPAK complex as an essential player in the control of DNA double-stranded break (DSB) repair and genomic stability. Specifically, we found that the mammalian STE20-like protein kinases 1 and 2 (MST1/2), independent of classical Hippo signaling, directly phosphorylated zinc finger MYND type-containing 8 (ZMYND8) and hence resulted in the suppression of DNA repair in the nucleus. In response to genotoxic stress, the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway was determined to relay nuclear DNA damage signals to the dynamic assembly of Hippo-STRIPAK via TANK-binding kinase 1-induced (TBK1-induced) structural stabilization of the suppressor of IKBKE 1- sarcolemma membrane-associated protein (SIKE1-SLMAP) arm. As such, we found that STRIPAK-mediated MST1/2 inactivation increased the DSB repair capacity of cancer cells and endowed these cells with resistance to radio- and chemotherapy and poly(ADP-ribose)polymerase (PARP) inhibition. Importantly, targeting the STRIPAK assembly with each of 3 distinct peptide inhibitors efficiently recovered the kinase activity of MST1/2 to suppress DNA repair and resensitize cancer cells to PARP inhibitors in both animal- and patient-derived tumor models. Overall, our findings not only uncover what we believe to be a previously unrecognized role for STRIPAK in modulating DSB repair but also provide translational implications of cotargeting STRIPAK and PARP for a new type of synthetic lethality anticancer therapy.

NCAPG promotes the oncogenesis and progression of non-small cell lung cancer cells through upregulating LGALS1 expression.

BACKGROUND: Numerous common oncogenic driver events have been confirmed in non-small cell lung cancer (NSCLC). Although targeted therapy has revolutionized NSCLC treatment, some patients still do not respond. NCAPG, also known as non-SMC condensin I complex subunit G, was positively associated with proliferation and migration in several tumor types. METHODS: We used transcriptional sequencing and TCGA database analysis to identify NCAPG as a new therapeutic target for NSCLC. The oncogenic roles of NCAPG in NSCLC tumor growth and metastasis were detected in vitro and in vivo. Ncapg+/+ or Ncapg+/- mice with urethane treatment were analyzed for oncogenesis of NSCLC. RESULTS: We investigated NCAPG as a new oncogenic driver which promoted NSCLC tumorigenesis and progression. We used transcriptome sequencing and the Cancer Genome Atlas (TCGA) database analysis to screen and found that NCAPG was negatively correlated with NSCLC survival. Using immunohistochemistry, we demonstrated that NCAPG overexpression was an independent risk factor for NSCLC survival. Functionally, NCAPG knockdown inhibited proliferation, migration, and invasion of NSCLC cells in vitro and in vivo. We exposed wildtype or Ncapg+/- mice to urethane and discovered that urethane-induced lung tumors were reduced in Ncapg+/- mice. Mechanistically, the function of NCAPG in promoting initiation and progression of NSCLC was closely related to LGALS1, which was also upregulated in NSCLC and might interact directly with NCAPG. CONCLUSIONS: This study indicates that NCAPG is one of the essential factors for NSCLC oncogenesis and progression, providing a new target for prognosis prediction and treatment of NSCLC.

[Regulation of the ubiquitin-proteasome system in spermiogenesis].

The ubiquitin-proteasome system (UPS) is an adenosine triphosphate (ATP)-dependent enzymatic machinery that targets substrate proteins for degradation by the 26S proteasome by tagging them with an isopeptide chain composed of covalently linked molecules of ubiquitin, a small chaperone protein. UPS is the main pathway of protein degradation in eukaryotic cells, and plays an important role in spermatogenesis. The dysfunction of various ubiquitin systems results in impaired sperm development with abnormal morphology and function, which is highly associated with male infertility. This review focuses on the roles of UPS in histone-to-protamine exchange, acrosome formation, sperm mitochondrial degradation and regulation of sperm function and quality.

The complete mitochondrial genome and phylogenetic analysis of Yanglong yak (Bos grunniens).

In this study, we assembled the complete mitochondrial genome of Yanglong yak (Bos grunniens) from Illumina sequencing reads. The mitochondrial genome is 16,323 bp long with an A + T-biased nucleotide composition, and encodes 13 protein-coding, 22 tRNA, and two rRNA genes along with a noncoding control region. In addition, its gene order is identical to those of the previously published mitochondrial genomes of its congeners. Phylogenetic analysis indicates that this breed is closely related to Datong yak, Pamir yak, Tianjun yak, polled yak, Seron yak, Sunnan yak, a series of Domestic Yak and wild yak, followed by Jinchuan yak and Gannan yak, and slightly far away from Bison and Bos taurus.

Characterization of the complete mitochondrial genome of the Dayu yak (Bos grunniens).

Dayu yak (Bos grunniens) is a long-furred yak breed from the Qinghai-Tibetan Plateau, and is highly adapted to local high-altitude and cold environments. In this study, its mitochondrial genome was characterized via high-throughput sequencing technology. The genome is 16,323 bp long with an AT-biased base composition (61.0% A + T; light strand), and harbors the typical set of 37 mitochondrial genes and a noncoding control region. Its gene arrangement is identical to those of other bovid taxa. Phylogenetic analysis suggests that Dayu yak is most closely related to Maiwa, Niangya, Qinghai Plateau, Xueduo and Yushu yaks.

Trends in Incidence and Survival of Patients with Pancreatic Neuroendocrine Neoplasm, 1987-2016.

BACKGROUND: Pancreatic neuroendocrine neoplasm (pNEN), with the lowest 5-year survival rates in neuroendocrine tumors (NETs), exerts great threat to human health. Because large-scale population research aimed at pNEN is rare, we aimed to explore the tendencies and differences of changes in incidences and survival rates of pNEN in each decade from 1987 to 2016 and evaluate the impacts of age, sex, race, socioeconomic status (SES), and grade. METHODS: Data on pNEN cases from 1987 to 2016 were extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier, Cox proportional hazards regression analyses, and relative survival rates (RSRs) were used to identify risk factors for pNEN. RESULTS: The incidence and survival duration of pNEN increase every decade due to medical developments. The disparities of long-term survival in different age, sex, and grade groups expanded over time while that in race and SES groups narrowed. Older age and higher grade are independent risk factors for poorer survival. Females have lower incidence and longer survival than males. Prognosis of Black patients and poor (medium and high poverty) patients improved. CONCLUSIONS: This study depicted changes in incidence and survival rates of pNEN over the past three decades and evaluated potential risk factors related to pNEN, benefiting future prediction of vulnerable and clinical options.

cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma by repressing RKIP.

Increasing evidence indicates that c-mesenchymal-epithelial transition factor (cMET) plays an important role in the malignant progression of colorectal cancer (CRC). However, the underlying mechanism is not fully understood. As a metastasis suppressor, raf kinase inhibitory protein (RKIP) loss has been reported in many cancer types. In this study, the expression levels of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored in vitro and in vivo. Our results showed that cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation indicated poor clinical outcomes. Moreover, the MAPK/ERK signaling pathway was implicated in the regulation of cMET and RKIP. Overexpression of cMET promoted tumor cell epithelial-mesenchymal transition, invasion, migration, and chemoresistance, whereas the effects could be efficiently inhibited by increased RKIP. Notably, small hairpin RNA-mediated cMET knockdown dramatically suppressed cell proliferation, although no RKIP-induced influence on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting the antioncogene RKIP, providing preclinical justification for targeting RKIP to treat cMET-induced metastasis of CRC.

DNASE1L3 as an indicator of favorable survival in hepatocellular carcinoma patients following resection.

Hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis. It is of great importance to identify biomarkers for the prediction of patients' survival.The mRNA expression level of deoxyribonuclease 1 like 3 (DNASE1L3) and its correlation with survival were accessed in 424 samples from The Cancer Genome Atlas database. Its expression level was confirmed by real-time quantitative polymerase chain reaction and western blotting in 20 pairs of postsurgical specimens. In addition, immunohistochemistry staining of DNASE1L3 was also performed in 113 postoperative samples, using a histochemistry score system. The relationship between patients' survival and DNASE1L3 expression level was evaluated by the Kaplan-Meier method.DNASE1L3 is downregulated in both mRNA and protein levels in HCC tissues, compared with adjacent normal tissues. 52 of 113 HCC specimens showed positive DNASE1L3 protein expression. Patients with positive DNASE1L3 expression had significantly longer overall survival, compared with patients with negative expression (p = 0.023). However, the DNASE1L3 fails to discriminate progression-free survival (p = 0.134). Multivariate COX analysis revealed that positive DNASE1L3 expression and higher differentiation were significantly associated with better overall survival.This study demonstrated that positive DNASE1L3 expression is an independent prognostic factor for better survival in HCC patients following radical resection.