Prognostic value of inflammation-based indices in patients with resected hepatocellular carcinoma.

BACKGROUND: As is well recognized that inflammation plays a crucial role in the genesis and progression of various cancer. Here we investigate the prognostic value of a novel index: the combination of neutrophil to lymphocyte ratio and platelet distribution width (coNLR-PDW) in post-operation patients with resectable hepatocellular carcinoma (HCC). METHODS: The receiver operating characteristic (ROC) curve was utilized to determine the optimal cutoff values of continuous variables, including the neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW). Kaplan-Meier method and the Log-rank test were used to compare survival differences across three groups stratified by the coNLR-PDW score. Univariate and multivariate Cox proportional hazard regression analyses were adopted to identify independent factors of HCC patient's prognosis. RESULTS: 1.59 and 13.0 were perceived as the optimal cutoff value for NLR and PDW based on the ROC curve, respectively. Kaplan-Meier method revealed that a higher coNLR-PDW score predicts poorer overall survival (OS) and disease-free survival (DFS) (P < 0.001). coNLR-PDW was demonstrated as an independent factor for both OS and DFS using Cox regression analysis in training and validation cohort. CONCLUSION: coNLR-PDW is recognized as a valuable biomarker for predicting the survival of patients with HCC.

ZEB1 serves an oncogenic role in the tumourigenesis of HCC by promoting cell proliferation, migration, and inhibiting apoptosis via Wnt/ß-catenin signaling pathway.

Zinc finger E-box-binding homeobox 1 (ZEB1), a functional protein of zinc finger family, was aberrant expressed in many kinds of liver disease including hepatic fibrosis and Hepatitis C virus. Bioinformatics results showed that ZEB1 was abnormally expressed in HCC tissues. However, to date, the potential regulatory role and molecular mechanisms of ZEB1 are still unclear in the occurrence and development of HCC. This study demonstrated that the expression level of ZEB1 was significantly elevated both in liver tissues of HCC patients and cell lines (HepG2 and SMMC-7721 cells). Moreover, ZEB1 could promote the proliferation, migration, and invasion of HCC cells. On the downstream regulation mechanism, ZEB1 could activate the Wnt/ß-catenin signaling pathway by upregulating the protein expression levels of ß-catenin, c-Myc, and cyclin D1. Novel studies showed that miR-708 particularly targeted ZEB1 3'-UTR regions and inhibited the HCC cell proliferation, migration, and invasion. Furthermore, results of nude mice experiments of HCC model indicated that miR-708 could inhibit tumor growth and xenograft metastasis model was established to validate that miR-708 could inhibit HCC cell metastasis through tail-vein injection in vivo. Together, the study suggested that ZEB1 modulated by miR-708 might be a potential therapeutic target for HCC therapy.

LMNB2 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested Lamin B2 (LMNB2) as an oncogene in lung cancer. However, the role of LMNB2 in hepatocellular carcinoma (HCC) remains unclear. METHOD: The expression of LMNB2 was compared between HCC samples and non-tumor samples in multiple datasets. In addition, the prognostic value of LMNB2 in HCC was also investigated. Furthermore, the cBioPortal was utilized to analyze the genomic alternation of LMNB2 in HCC. Besides, co-expression genes and functional enrichment analysis were evaluated using LinkedOmics to determine the function of LMNB2. Finally, the correlation between LMNB2 and immune infiltration was assessed using Tumor Immune Estimation Resource (TIMER). RESULTS: Elevated LMNB2 expression level was identified in HCC patients in multiple datasets. Moreover, increased levels of LMNB2 were associated with poor overall survival (OS) and disease-free survival (DFS). The functional enrichment analysis revealed that LMNB2 plays an essential role via the cell cycle pathway, spliceosome, hippo-signaling pathway, and metabolic pathways. Besides, copy number variation (CNV) and methylation were significantly associated with LMNB2 expression. Additionally, increased levels of LMNB2 were significantly associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. CONCLUSION: LMNB2 is a potential HCC prognostic and diagnostic biomarker.

The Prognostic Role of a Combined Fibrinogen and Neutrophil-to-Lymphocyte Ratio Score in Patients with Resectable Hepatocellular Carcinoma: A Retrospective Study.

BACKGROUND Inflammation and activation of the coagulation cascades have a role in the pathogenesis of malignancy, including hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic role of the combined fibrinogen and neutrophil-to-lymphocyte ratio (F-NLR) in patients with resectable HCC. MATERIAL AND METHODS This retrospective study included 292 patients with HCC who underwent surgical resection. The receiver operating characteristic (ROC) curve was used to determine the cut-off value of preoperative fibrinogen (Fib) levels and the neutrophil-to-lymphocyte ratio (NLR). The. Hyperfibrinogenemia was >3.35 g/L, and an increased NLR was ≥2.47. The F-NLR was calculated for all patients. Kaplan-Meier survival curves, univariate analysis, multivariate analysis, and subgroup analysis were used to identify independent prognostic factors for overall survival (OS) and disease-free survival (DFS). The receiver operating characteristic (ROC) curve analysis of the F-NLR score and OS, according to the Barcelona Clinic Liver Cancer (BCLC) stage, was performed. RESULTS Increased F-NLR scores were significantly associated with the presence of tumor thrombus (P=0.001), larger tumor diameter (P<0.001), vascular invasion (P<0.001), and increased BCLC stage (P<0.001). Multivariate analysis showed that the F-NLR score was an independent predictor of OS (P<0.001) and DFS (P=0.002). The prognostic role of F-NLR was significant for BCLC stage 0-I (P=0.004; P<0.001) and BCLC stage II-III (P=0.026; P=0.005) for OS and DFS, respectively. CONCLUSIONS In patients with resectable HCC, the combined F-NLR score, a new indicator of systemic inflammation, was an independent prognostic indicator.

Investigation of Novel Pesticides with Insecticidal and Antifungal Activities: Design, Synthesis and SAR Studies of Benzoylpyrimidinylurea Derivatives.

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by ¹H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 µg mL-1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg mL-1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.

A pan-cancer analysis uncovering the function of CRHBP in tumor immunity, prognosis and drug response: especially its function in LIHC.

Corticotropin-releasing hormone-binding protein (CRHBP) is involved in many physiological processes. However, it is still unclear what role CRHBP has in tumor immunity and prognosis prediction. Using databases such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Protein Database, Timer Database, and Gene Expression Profiling Interactive Analysis (GEPIA), we evaluated the potential role of CRHBP in diverse cancers. Further research looked into the relationships between CRHBP and tumor survival prognosis, immune infiltration, immune checkpoint (ICP) indicators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methylation, tumor microenvironment (TME), and drug responsiveness. The anticancer effect of CRHBP in liver hepatocellular carcinoma (LIHC) was shown by Western blotting, EdU staining, JC-1 staining, transwell test, and wound healing assays. CRHBP expression is significantly low in the majority of tumor types and is associated with survival prognosis, ICP markers, TMB, and microsatellite instability (MSI). The expression of CRHBP was found to be substantially related to the quantity of six immune cell types, as well as the interstitial and immunological scores, showing that CRHBP has a substantial impact in the TME. We also noticed a link between the IC50 of a number of anticancer medicines and the degree of CRHBP expression. CRHBP-related signaling pathways were discovered using functional enrichment. Cox regression analysis showed that CRHBP expression was an independent prognostic factor for LIHC. CRHBP has a tumor suppressor function in LIHC, according to cell and molecular biology trials. CRHBP has a significant impact on tumor immunity, treatment, and prognosis, and has the potential as a cancer treatment target and prognostic indicator.

TMF inhibits extracellular matrix degradation by regulating the C/EBPß/ADAMTS5 signaling pathway in osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease, characterized by degenerative destruction of articular cartilage. Chondrocytes, the unique cell type in cartilage, mediate the metabolism of extracellular matrix (ECM), which is mainly constituted by aggrecan and type II collagen. A disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5) is an aggrecanase responsible for the degradation of aggrecan in OA cartilage. CCAAT/enhancer binding protein ß (C/EBPß), a transcription factor in the C/EBP family, has been reported to mediate the expression of ADAMTS5. Our previous study showed that 5,7,3',4'-tetramethoxyflavone (TMF) could activate the Sirt1/FOXO3a signaling in OA chondrocytes. However, whether TMF protected against ECM degradation by down-regulating C/EBPß expression was unknown. In this study, we found that aggrecan expression was down-regulated, and ADAMTS5 expression was up-regulated. Knockdown of C/EBPß could up-regulate aggrecan expression and down-regulate ADAMTS5 expression in IL-1ß-treated C28/I2 cells. TMF could compromise the effects of C/EBPß on OA chondrocytes by activating the Sirt1/FOXO3a signaling. Conclusively, TMF exhibited protective activity against ECM degradation by mediating the Sirt1/FOXO3a/C/EBPß pathway in OA chondrocytes.

Advances in the roles of ATF4 in osteoporosis.

Osteoporosis (OP) is characterized by reduced bone mass, decreased strength, and enhanced bone fragility fracture risk. Activating transcription factor 4 (ATF4) plays a role in cell differentiation, proliferation, apoptosis, redox balance, amino acid uptake, and glycolipid metabolism. ATF4 induces the differentiation of bone marrow mesenchymal stem cells (BM-MSCs) into osteoblasts, increases osteoblast activity, and inhibits osteoclast formation, promoting bone formation and remodeling. In addition, ATF4 mediates the energy metabolism in osteoblasts and promotes angiogenesis. ATF4 is also involved in the mediation of adipogenesis. ATF4 can selectively accumulate in osteoblasts. ATF4 can directly interact with RUNT-related transcription factor 2 (RUNX2) and up-regulate the expression of osteocalcin (OCN) and osterix (Osx). Several upstream factors, such as Wnt/ß-catenin and BMP2/Smad signaling pathways, have been involved in ATF4-mediated osteoblast differentiation. ATF4 promotes osteoclastogenesis by mediating the receptor activator of nuclear factor κ-B (NF-κB) ligand (RANKL) signaling. Several agents, such as parathyroid (PTH), melatonin, and natural compounds, have been reported to regulate ATF4 expression and mediate bone metabolism. In this review, we comprehensively discuss the biological activities of ATF4 in maintaining bone homeostasis and inhibiting OP development. ATF4 has become a therapeutic target for OP treatment.

Geniposide stimulates autophagy by activating the GLP-1R/AMPK/mTOR signaling in osteoarthritis chondrocytes.

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degeneration. Autophagy is associated with chondrocyte homeostasis and exhibits a role in protecting against OA pathogenesis. Geniposide (GEN), an iridoid glycoside extracted from Eucommia ulmoides Oliv, acts as an activator of GLP-1R, which can stimulate autophagy. The AMPK/mTOR signaling pathway participates in the mediation of autophagy, and GLP-1R may act as an upstream factor of AMPK. However, whether GEN mediates the autophagic responses by activating the GLP-1R/AMPK/mTOR signaling pathway in OA chondrocytes is still unclear. In the current study, attenuated autophagy in MIA-induced rat OA models was observed, as shown by up-regulated expression of p62 and down-regulated expression of Beclin-1 and LC3-II/I. GEN stimulated autophagy and protected OA cartilage by up-regulating GLP-1R expression. In addition, GEN could enhance AMPK phosphorylation and down-regulate mTOR expression in IL-1ß-treated C28/I2 cells. Inhibition of AMPK or activation of mTOR could reverse the stimulatory effects of GEN on autophagy. Furthermore, a GLP-1R inhibitor Exendin 9-39 could eliminate the chondroprotective effects of GEN by suppressing the AMPK/mTOR signaling pathway. Conclusively, Geniposide exhibits protective effects against osteoarthritis development by stimulating autophagy via activating the GLP-1R/AMPK/mTOR signaling pathway.

C/EBPß: The structure, regulation, and its roles in inflammation-related diseases.

Inflammation, a mechanism of the human body, has been implicated in many diseases. Inflammatory responses include the release of inflammatory mediators by activating various signaling pathways. CCAAT/enhancer binding protein ß (C/EBPß), a transcription factor in the C/EBP family, contains the leucine zipper (bZIP) domain. The expression of C/EBPß is mediated at the transcriptional and post-translational levels, such as phosphorylation, acetylation, methylation, and SUMOylation. C/EBPß has been involved in inflammatory responses by mediating several signaling pathways, such as MAPK/NF-κB and IL-6/JAK/STAT3 pathways. C/EBPß plays an important role in the pathological development of inflammation-related diseases, such as osteoarthritis, pneumonia, hepatitis, inflammatory bowel diseases, and rheumatoid arthritis. Here, we comprehensively discuss the structure and biological effects of C/EBPß and its role in inflammatory diseases.

The RAGE signaling in osteoporosis.

Osteoporosis (OP), characterized by an imbalance of bone remodeling between formation and resorption, has become a health issue worldwide. The receptor for advanced glycation end product (RAGE), a transmembrane protein in the immunoglobin family, has multiple ligands and has been involved in many chronic diseases, such as diabetes and OP. Increasing evidence shows that activation of the RAGE signaling negatively affects bone remodeling. Ligands, such as advanced glycation end products (AGEs), S100, ß-amyloid (Aß), and high mobility group box 1 (HMGB1), have been well documented that they may negatively regulate the proliferation and differentiation of osteoblasts and positively stimulate osteoclastogenesis by activating the expression of RAGE. In this review, we comprehensively discuss the structure of RAGE and its biological functions in the pathogenesis of OP. The research findings suggest that RAGE signaling has become a potential target for the therapeutic management of OP.

Cleavage Stimulation Factor Subunit 2: Function Across Cancers and Potential Target for Chemotherapeutic Drugs.

The cleavage stimulation factor subunit complex is involved in the cleavage and polyadenylation of 3'-end pre-mRNAs that regulate mRNA formation and processing. However, cleavage stimulation factor subunit 2 (CSTF2) was found to play a more critical regulatory role across cancers. General cancer data sets from The Cancer Genome Atlas and Genotype-Tissue Expression project were thus downloaded for differential analysis, and the possible functions and mechanisms of CSTF2 in general cancer were analyzed using the Compartments database, cBioPortal database, Tumor Immune Single-cell Hub database, and Comparative Toxigenomics database using gene set enrichment analysis and R software. The results showed that CSTF2 could affect DNA repair and methylation in tumor cells. In addition, CSTF2 was associated with multiple tumor immune infiltrates in a wide range of cancers, and its high expression was associated with multiple immune checkpoints; therefore, it could serve as a potential target for many drug molecules. We also proved that CSTF2 promotes oral cell proliferation and migration. The high diagnostic efficacy of CSTF2 suggested that this gene may act as a new biomarker and personalized therapeutic target for a variety of tumors.

An m6A-Related lncRNA Signature Predicts the Prognosis of Hepatocellular Carcinoma.

Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC). Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature. Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency. Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.

A Novel Epithelial-Mesenchymal Transition Gene Signature Correlated With Prognosis, and Immune Infiltration in Hepatocellular Carcinoma.

Background: Although many genes related to epithelial-mesenchymal transition (EMT) have been explored in hepatocellular carcinoma (HCC), their prognostic significance still needs further analysis. Methods: Differentially expressed EMT-related genes were obtained through the integrated analysis of 4 Gene expression omnibus (GEO) datasets. The univariate Cox regression and Lasso Cox regression models are utilized to determine the EMT-related gene signature. Based on the results of multivariate Cox regression, a predictive nomogram is established. Time-dependent ROC curve and calibration curve are used to show the distinguishing ability and consistency of the nomogram. Finally, we explored the correlation between EMT risk score and immune immunity. Results: We identified a nine EMT-related gene signature to predict the survival outcome of HCC patients. Based on the EMT risk score's median, HCC patients in each dataset were divided into high and low-risk groups. The survival outcomes of HCC patients in the high-risk group were significantly worse than those in the low-risk group. The prediction nomogram based on the EMT risk score has better distinguishing ability and consistency. High EMT risk score was related to immune infiltration. Conclusion: The nomogram based on the EMT risk score can reliably predict the survival outcome of HCC patients, thereby providing benefits for medical decisions.

A Pan-Cancer Analysis of the Oncogenic Role of Cell Division Cycle-Associated Protein 4 (CDCA4) in Human Tumors.

PURPOSE: To unravel the oncogenic role of CDCA4 in different cancers from the perspective of tumor immunity. METHODS: Raw data on CDCA4 expression in tumor samples and paracancerous samples were obtained from TCGA and GTEX databases. In addition, we investigated pathological stages and the survival analysis of CDCA4 in pan-cancer across Gene Expression Profiling Interactive Analysis (GEPIA) database. Cox Proportional Hazards Model shows that high CDCA4 levels are associated with several vital indicators in oncology. On the one hand, we explored the correlation between CADA4 expression and tumor immune infiltration by the TIMER tool; On the other hand, we utilized the methods of CIBERSORT and ESTIMATE computational to evaluate the proportion of tumor infiltrating immune cells (TIIC) and the amounts of stromal and immune components based on TCGA database. The use of antineoplastic drugs and the expression of CDCA4 also showed a high correlation via linear regression. Protein-Protein Interaction analysis was performed in the GeneMANIA database, and enrichment analysis was performed and predicted signaling pathways were identified by using Gene Ontology and Kyoto Encyclopedia of Genes. The correlation between CDCA4 expression with Copy number variations (CNV) and methylation is detailed, respectively. Molecular biology experiments including Western blotting, flow cytometry, EDU staining, Transwell and Wound Healing assay to validate the cancer promoting role of CDCA4 in hepatocellular carcinoma (HCC). RESULTS: Most tumors highly expressed CDCA4. Elevated CDCA4 expression was associated with poor OS and DFS. There was a significant correlation between CDCA4 expression and TITCs. Moreover, markers of TIICs exhibited distinct patterns of CDCA4 associated immune infiltration. In addition, we pay attention to the association between the expression of CDCA4 and the use of the anti-tumor drugs. CDCA4 is related to biological progress (BP), cellular component (CC) and molecular function (MF). Dopaminergic Synapse, AMPK, Sphingolipid, Chagas Disease, mRNA Surveillance were significantly enriched pathways in positive and negative correlation genes with CDCA4. CNV is thought to be a positive correlation with CDCA4 expression. Conversely, methylation is negative correlation with CDCA4 expression. Molecular biology experiments confirm a cancer promoting role for CDCA4 in HCC. CONCLUSION: CDCA4 may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new way of thinking for cancer treatment.

Prognostic value of CD169-positive macrophages in various tumors: a meta-analysis.

The study aimed to evaluate the prognostic value of CD169 expression in tumor-infiltrating macrophages from regional lymph nodes (RLN) in various tumors. In order to identify eligible articles, PubMed, EMBASE, Web of Science, and Cochrane Library were used to conduct a systematic search. Pooled hazard ratios (HRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were adopted to assess the relationship between CD169 expression and overall survival (OS) and clinicopathological characteristics. Ten studies, including eleven cohorts with 1699 patients, were enrolled. We found that high CD169+ expression in tumor-infiltrating macrophages from RLN was associated with a favorable OS (HR = 0.56, 95%CI: 0.39-0.79, P = 0.001). Subgroup analysis showed that high CD169+ expression had more predictive power in digestive system tumors (HR = 0.52, 95%CI: 0.42-0.67, <0.001). In addition, high CD169 expression was significantly linked with lymph node metastasis (OR = 0.66, 95%CI: 0.47-0.94, P = 0.020) and TNM stage (OR = 0.62, 95%CI: 0.48-0.80, P < 0.001). High CD169 expression in tumor-infiltrating macrophages from RLN was correlated with favorable survival outcome in patients with malignancies. CD169 may be a novel and effective prognostic marker, especially for digestive system tumors.

Diagnostic Value of Serum D-Dimer for Detection of Gallbladder Carcinoma.

BACKGROUND: Previous studies have shown that D-dimer plays an essential role in the occurrence and development of various tumors, and its diagnostic value in gallbladder carcinoma (GBC) is unknown. Therefore, the purpose of our study was to explore the diagnostic value of D-dimer in distinguishing between gallbladder carcinoma and benign controls. METHODS: We retrospectively included age and gender-matched patients with gallbladder carcinoma and benign gallbladder lesions, and analyzed the diagnostic value of inflammatory markers, D-dimers, and tumor biomarkers by receiver operating characteristic curves (ROC). RESULTS: The area under the ROC curve of white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), D-dimer, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were 0.600, 0.760, 0.729, 0.849, 0.502, 0.699, and 0.802, respectively. The combined diagnostic value of D-dimer and CA19-9 was 0.920, which was superior to other joint indicators. CONCLUSION: Serum D-dimer may be considered as a potential biomarker for detection of GBC. Moreover, the combined diagnosis of D-dimer and CA19-9 has excellent diagnostic value in gallbladder carcinoma.

A Novel Nine-Gene Signature Associated With Immune Infiltration for Predicting Prognosis in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its prognosis remains unsatisfactory. The identification of new and effective markers is helpful for better predicting the prognosis of patients with HCC and for conducting individualized management. The oncogene Aurora kinase A (AURKA) is involved in a variety of tumors; however, its role in liver cancer is poorly understood. The aim of this study was to establish AURKA-related gene signatures for predicting the prognosis of patients with HCC. Methods: We first analyzed the expression of AURKA in liver cancer and its prognostic significance in different data sets. Subsequently, we selected genes with prognostic value related to AURKA and constructed a gene signature based on them. The predictive ability of the gene signature was tested using the HCC cohort development and verification data sets. A nomogram was constructed by integrating the risk score and clinicopathological characteristics. Finally, the influence of the gene signature on the immune microenvironment in HCC was comprehensively analyzed. Results: We found that AURKA was highly expressed in HCC, and it exhibited prognostic value. We selected eight AURKA-related genes with prognostic value through the protein-protein interaction network and successfully constructed a gene signature. The nine-gene signature could effectively stratify the risk of patients with HCC and demonstrated a good ability in predicting survival. The nomogram showed good discrimination and consistency of risk scores. In addition, the high-risk group showed a higher percentage of immune cell infiltration (i.e., macrophages, myeloid dendritic cells, neutrophils, and CD4+T cells). Moreover, the immune checkpoints SIGLEC15, TIGIT, CD274, HAVCR2, and PDCD1LG2 were also higher in the high-risk group versus the low-risk group. Conclusions: This gene signature may be useful prognostic markers and therapeutic targets in patients with HCC.

Development and Validation of an Autophagy-Related Gene Signature for Predicting the Prognosis of Hepatocellular Carcinoma.

PURPOSE: Autophagy is a lysosomal degradation pathway that is essential for maintaining the homeostasis of the intracellular environment. Mounting evidence indicates that autophagy plays an essential role in the occurrence and development of hepatocellular cancer (HCC). This research is aimed at exploring the prognostic value of autophagy-related genes (ARGs) in HCC patients. METHODS: The Wilcoxon test was used to identify differentially expressed ARGs in The Cancer Genome Atlas (TCGA) HCC cohort. Then, the TCGA cohort was randomly divided into training and testing groups. Cox and LASSO regression models were used to screen for autophagy-related genes that affect overall survival (OS) in the TCGA training group. Based on the coefficient of risk genes, we constructed an autophagy-related gene signature for predicting the prognosis of HCC patients. Finally, we validated the prognostic significance of autophagy-related gene signature using the TCGA testing group and three external datasets. RESULTS: ATG10, BIRC5, GAPDH, and TMEM74 are risk genes for OS. According to the optimal cutoff value of risk score in each HCC dataset, HCC patients can divide into high- and low-risk groups. ARG risk score can significantly distinguish HCC patients with different survival outcomes. Meanwhile, the ARG risk score is independently correlated with OS in multiple HCC cohorts. CONCLUSIONS: The autophagy-related risk score can effectively screen high-risk HCC patients and provide guidance for clinical prevention and treatment of HCC.

ABL1 Is a Prognostic Marker and Associated with Immune Infiltration in Hepatocellular Carcinoma.

BACKGROUND: The role of ABL1 in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the potential role of ABL1 in the progression of HCC using bioinformatics methods. METHODS: We analyzed the expression, prognostic potential, and immune cell effect of ABL1 in HCC by using a variety of datasets. RESULTS: ABL1 is highly expressed in HCC and associated with unfavorable overall survival (OS) and disease-free survival (DFS). Functional network analysis revealed that ABL1 plays an important role in mitochondrial activity, ATP metabolism, protein translation and metabolism, various neurological diseases, nonalcoholic fatty liver disease, and notch signaling pathway. In addition, we found that ABL1 expression was closely correlated with B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, ABL1 expression was positively associated with the expression levels of immune checkpoint genes, such as PD-1L, TIM3, TIGIT, and CTLA4. CONCLUSION: ABL1 is associated with immune infiltration and prognosis of HCC.