Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma.

Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

Correlation between ABO blood group and prognosis of hepatectomy for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: The relationship between ABO blood group and prognosis of patients with hepatocellular carcinoma (HCC) remains unclear. We investigated the relationship between prognosis and ABO blood group in patients with hepatitis B-associated HCC after radical hepatectomy. METHODS: The medical records of 874 patients with hepatitis B-associated HCC who underwent radical liver tumor resection were retrospectively collected. Cox proportional risk models were constructed for analysis, and the patient data were further balanced using propensity score matching (PSM) analysis to assess the impact of ABO blood group on the prognosis of patients with hepatitis B-associated HCC. RESULTS: In univariate Cox regression analysis, the overall survival (OS) of non-A blood type group vs. A blood type group [hazard ratio (HR) (95% confidence interval [CI]) = 1.504 (1.003-2.255), P = 0.048], in multivariate Cox regression analysis the OS of non-A blood type group versus A blood type group [HR (95% CI) = 1.596 (1.054-2.417), P = 0.027]. After PSM, the baseline information was more balanced between the two groups, yielding the same results as above [HR (95% CI) = 1.550 (1.012-2.373), P = 0.044]. CONCLUSION: The difference in OS after radical hepatectomy in patients with hepatitis B-associated HCC was statistically significant in terms of ABO blood group, OS was lower in patients with non-A blood group than in patients with A blood group.

Comprehensive analysis of LILR family genes expression and tumour-infiltrating immune cells in early-stage pancreatic ductal adenocarcinoma.

Leucocyte immunoglobulin-like receptors (LILRs) are closely related to tumourigenesis, but their clinical value in early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy remains unknown. Kaplan-Meier and Cox proportional hazards regression models is used to investigate the association between LILR expression and prognosis in tumour biopsies and peripheral blood mononuclear cells. Risk score was calculated for each patient based on the prognostic model. DAVID, STRING, GeneMANIA, and GSEA were used to conduct pathway and functional analyses. The CIBERSORT algorithm is used to analyse tumour-infiltrating immune cells. Survival analysis showed that high levels of LILRA4 (p = 0.006) and LILRB4 (p = 0.04) were significantly associated with better overall survival. High levels of LILRA2 (p = 0.008) and LILRB4 (p = 0.038) were significantly associated with better relapse-free survival. JAK-STAT signalling pathway, regulation of T cell activation, regulation of the immune effector process, and tumour necrosis factor superfamily cytokine production were involved in molecular mechanisms that affected poor prognoses in the high-risk group in GSEA. CIBERSORT demonstrated that the high-risk group had significantly higher infiltrating fraction of memory-activated CD4 T cells and activated NK cells and lower fraction of resting dendritic cells and neutrophils. LILRB4 plays crucial roles in affecting the clinical outcomes of early-stage PDAC.

A pan-cancer analysis of the expression and prognostic significance of PDRG1.

Background: PDRG1 are involved in various physiological regulations of cells, include cell proliferation, growth, apoptosis and cell cycle regulation, but their roles in cancer have not been clearly studied. Methods: Firstly, we evaluated the expression and prognostic significance of PDRG1 using a pan-cancer analysis of The Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. Secondly, correlations between PDRG1 and pan-cancer immune cells, m6A methylation, tumor mutation burden (TMB), and microsatellite instability (MSI) were investigated. Finally, we explored the relationship between PDRG1 expression and clinical stage in hepatocellular carcinoma (HCC). Results: We found that PDRG1 was significantly overexpressed in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC), and other tumor tissues and was associated with prognosis. In addition, PDRG1 was closely associated with pan-cancer immune cells, m6A methylation, TMB, and MSI expression. The expression of PDRG1 in HCC was correlated with clinical stage, and western blot assay confirmed that PDRG1 was significantly overexpressed in HCC tissues. Conclusions: PDRG1 may be an important pan-cancer molecular biomarker for diagnosis and prognosis, and our results may provide a theoretical basis for its future clinical application in cancer diagnosis, treatment, and prognosis, and have been preliminarily validated in HCC.

Recurrence of Early Hepatocellular Carcinoma after Surgery May Be Related to Intestinal Oxidative Stress and the Development of a Predictive Model.

Background: Early stage hepatocellular carcinoma (HCC) has a high recurrence rate after surgery and lacks reliable predictive tools. We explored the potential of combining enhanced CT with gut microbiome to develop a predictive model for recurrence after early HCC surgery. Methods: A total of 112 patients with early HCC who underwent hepatectomy from September 2018 to December 2020 were included in this study, and the machine learning method was divided into a training group (N = 71) and a test group (N = 41) with the observed endpoint of recurrence-free survival (RFS). Features were extracted from the arterial and portal phases of enhanced computed tomography (CT) images and gut microbiome, and features with minimum absolute contraction and selection operator regression were created, and the extracted features were scored to create a preoperative prediction model by using the multivariate Cox regression analysis with risk stratification analysis. Results: In the study cohort, the model constructed by combining radiological and gut flora features provided good predictive performance (C index, 0.811 (0.650-0.972)). The combined radiology and gut flora-based model constructed risk strata with high, intermediate, or low risk of recurrence and different characteristics of recurrent tumor imaging and gut flora. Recurrence of early stage hepatocellular carcinoma may be associated with oxidative stress in the intestinal flora. Conclusions: This study successfully constructs a risk model integrating enhanced CT and gut microbiome characteristics that can be used for the risk of postoperative recurrence in patients with early HCC. In addition, intestinal flora associated with HCC recurrence may be involved in oxidative stress.

Biomimetic cytomembrane-coated ZIF-8-loaded DMDD nanoparticle and sonodynamic co-therapy for cancer.

Background: Breast cancer (BC) is the most common type of cancer affecting females. It is also a leading cause of cancer-related death in women worldwide. Methods: Sonodynamic therapy (SDT) is an emerging therapeutic strategy for cancer treatment. SDT ensures non-invasive penetration of deep tumors and results in activation of non-toxic sonosensitizers administered in deep tumor sites to become cytotoxic. It has been reported that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has a significant anti-tumor effect against various cancer types including BC. However, DMDD is hydrophobic. Therefore, a one-step encapsulation method was used in the current study to construct zeolitic imidazole frameworks-8 (ZIF-8) loaded with DMDD and sonosensitizer chlorin e6 (Ce6). ZIF-8 was further modified by coating it with a biomimetic cell membrane to improve targeted delivery. Results: In vitro and in vivo results indicated that the nanomedicines had great biocompatibility properties and targeting ability. The nanocomposite exhibited a higher release rate under an acidic tumor microenvironment. The tumor killing effect of reactive oxygen species (ROS) generated from Ce6 and inhibition of tumor growth was enhanced after ultrasound (US) treatment, which might be caused by the increase in apoptosis rate. Conclusions: These findings show that the combination of nanomedicine and SDT provides a potential therapeutic method for BC.

A novel Peng's test in reducing bile leakage after partial hepatectomy for hepatocellular carcinoma: From an animal study to a clinical cohort Propensity score matching comparative study.

BACKGROUND: Bile leakage (BL) is a common complication of partial hepatectomy for hepatocellular carcinoma (HCC). However, various intraoperative approaches to detect BL have not been widely accepted owing to uncertainty in their treatment effectiveness and complexity of use. MATERIALS AND METHODS: A novel BL-detection approach (Peng's test) was developed in a swine model to determine the pressures generated in the gallbladder and common bile duct (CBD) during the test. A comparative study was then conducted on a prospective cohort of patients using Peng's test versus a retrospective historical cohort patient group using the White Gauze test in partial hepatectomy for HCC. Propensity score matching (PSM) was performed in a 1:1 ratio to balance confounding factors. RESULTS: The maximum pressures with methylene blue injection in the gallbladder and CBD without Pringle's maneuver in the four swines were 103.8 ± 11.8 and 42.3 ± 6.1, respectively. After Pringle's maneuver, 32.0 ± 6.8 mL methylene blue injection led to a maximum pressure in the CBD of 85.3 ± 9.5 cmH2O. The pressures in CBD were 25.8 ± 3.3 and 86.0 ± 9.9 cmH2O when BL appeared at small bile ducts and around the ligation sites, respectively. Of the 206 patients enrolled in the historical control group, 31 (15.0%) developed BL, while of the 54 patients in the study group, only 1 developed grade A BL. The number of BL detected by the routine white gauze test in the control group was significantly lower than that in the study group (Z = -3.002, P = 0.003). After PSM, the incidence of BL in the control group and grade B/C BL was 20.4% and 11.1%, respectively. The corresponding incidences in the study group were 1.9% (χ2 = 7.594, P = 0.006) and 0% (P = 0.027), respectively. The length of hospital stay in the study group was significantly reduced (Z = -6.048, P < 0.001). CONCLUSION: Peng's test for intraoperative BL detection is safe and effective in reducing BL after hepatectomy.

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione on autophagy and the PI3K/AKT/mTOR signaling pathway in human cholangiocarcinoma QBC939 cells.

Background: 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has been reported to have good antitumor effects. The aim of this study was to investigate whether DMDD induces apoptosis and autophagy in human cholangiocarcinoma (CCA) QBC939 cells and determine its effect on the PI3K/AKT/mTOR signaling pathway. Methods: QBC939 cells were cultured in vitro and changes in cell viability were detected by the Cell Counting Kit (CCK8) assay after treatment with different concentrations of DMDD for 24, 48, and 72 h. The cells were divided into control and DMDD-treated groups (treated concentrations were 10, 15, and 20 µM/L), and the cell cycle, apoptosis, and autophagic vesicles were assessed. The expression levels of PI3K, AKT, mTOR, microtubule-associated protein 1 light chain 3 beta (LC3-II)/I, Beclin-1, and P62 were detected by Western blot. A xenograft mouse model was constructed to detect the effect of DMDD on CCA. Results: The experimental results showed that DMDD was able to inhibit proliferation, migration, and invasion and induce cell cycle arrest and autophagy of QBC939 cells. In addition, DMDD decreased the protein expression of PI3K, AKT, and mTOR and increased the expression of LC3-II/I, Beclin-1, and P62. In mice, DMDD was able to inhibit the growth of tumors. Conclusions: DMDD inhibits CCA cell viability and induces cell cycle arrest and autophagy by a mechanism that may be related to the downregulation of the PI3K/AKT/mTOR signaling pathway.

Graft versus host disease after liver transplantation following radiotherapy for the treatment of hepatocellular carcinoma: A case report and literature review.

Graft versus host disease after solid organ transplantation is very rare. This article reports a case of graft versus host disease after liver transplantation following targeted therapy and radiotherapy for the treatment of hepatocellular carcinoma. The patient developed a symptomatic skin rash and pancytopenia 13 days after surgery, which was confirmed as graft versus host disease after liver transplantation by histopathology and fluorescence in situ hybridization. Early diagnosis of graft versus host disease after solid organ transplantation is difficult and often delayed due to nonspecific manifestations that overlap with other diseases. Currently, the treatment of graft versus host disease after liver transplantation occurs by either strengthening the immune suppression or weakening the immune suppression; however, there is no unified standard treatment strategy. We found that in addition to age, gender, and human leukocyte antigen type, preoperative radiotherapy is a likely risk factor for graft versus host disease after liver transplantation.

A comprehensive analysis of the diagnostic and prognostic value associated with the SLC7A family members in breast cancer.

Background: The solute carrier (SLC) 7 family genes play central roles in cancer cell metabolism as glucose and glutamate transporters. However, their expression and prognostic value in breast cancer (BC) remains to be elucidated. Methods: Clinical data from BC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Kaplan-Meier (KM) plotter database. The mechanisms underlying the association between SLC7A expression and overall survival (OS) were explored using Cox regression and log-rank tests. ESTIMATE gives a measure of the immune-cell infiltrates. Single-sample (ss) Gene Set Enrichment Analysis (GSEA) was conducted to quantify immune cell infiltration. Results: High SLC7A5 expression was associated with a poorer survival time in BC patients according to the TCGA and KM plotter data. SLC7A4 was associated with good progression-free interval (PFI) and disease-specific survival (DSS) according to the TCGA data. Furthermore, SLC7A4 was correlated with good prognosis of OS, distant metastasis-free survival (DMFS), relapse-free survival (RFS), and post-progression survival (PPS) according to the KM plotter data. SLC7A3 expression was positively associated with OS, but was not strongly associated with PFI nor DSS in the TCGA data. However, SLC7A3 was positively correlated with DMFS and RFS in the KM database analysis. SLC7A had excellent diagnostic value in BC patients and was strongly correlated with tumor infiltration. T helper 2 (Th2) cells, CD56 bright natural killer (NK) cells, and NK cells were the most strongly correlated with the SLC7A family genes, suggesting that these genes play a crucial role in BC partly by modulating immune infiltration. Conclusions: SLC7A4 and SLC7A5 expression levels may be sensitive biomarkers for predicting BC outcomes. SLC7A3 may be a potential diagnostic and prognostic biomarker in BC, but further studies are warranted to verify these results.

Down regulated oncogene KIF2C inhibits growth, invasion, and metastasis of hepatocellular carcinoma through the Ras/MAPK signaling pathway and epithelial-to-mesenchymal transition.

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer death. Kinesin family member 2C (KIF2C) has been shown as oncogene in a variety of tumors. However, its role in HCC remains unclear. Methods: In this study, the expression level of KIF2C in HCC was detected by immunohistochemical staining and RT-PCR, and verified by Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine database. A curve was established to evaluate the diagnostic efficiency of KIF2C. The effect of KIF2C on HCC was investigated by flow cytometry, Cell Counting Kit-8, Transwell, and the wound-healing assay. We explored the underlying mechanism through epithelial-to-mesenchymal transition (EMT) and transcriptome sequences analysis. Results: KIF2C was overexpression in HCC tissue and related to neoplasm histologic grade (P<0.001), pathology stage (P=0.001), and a dismal prognosis (overall, recurrence-free, and disease-free survival). The diagnostic efficacy of KIF2C was >90% in diagnosing HCC. The HCC cell function experiments showed that KIF2C promoted HCC cell proliferation, migration, invasion, and an accelerated cell cycle, and inhibited apoptosis. Based on western blot analysis and RT-PCR, we found that KIF2C promoted HCC invasion and metastasis through activation of the EMT. Based on transcriptome sequences, we showed that KIF2C promoted HCC through the Ras/MAPK and PI3K/Akt signaling pathway. Conclusions: KIF2C was found to promote the progression of HCC and is anticipated to serve as a biomarker for HCC diagnosis, prognosis, and targeted therapy.

Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy.

INTRODUCTION AND OBJECTIVES: Whether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy. PATIENTS AND METHODS: This retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence. RESULTS: Male patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084-2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093-2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215-2.936], P = 0.006), but not for late recurrence. CONCLUSIONS: There is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.

High-Mobility Group AT-Hook 1 Served as a Prognosis Biomarker and Associated with Immune Infiltrate in Hepatocellular Carcinoma.

BACKGROUND: The protein high-mobility group AT-hook 1 (HMGA1) has been demonstrated that modulated cellular proliferation, invasion, and apoptosis with a poor prognosis in miscellaneous carcinomas. However, the mechanism of circumstantial carcinogenesis and association with the immune microenvironment of HMGA1 in hepatocellular carcinoma (HCC) had not been extensively explored. METHODS: The gene expression, clinicopathological correlation, and prognosis analysis were performed in the data obtained from TCGA. The results were further validated by ICGC and GEO database and external validation cohort from Guangxi. The HMGA1 protein expression was further examined in the HPA database. Biological function analyses were conducted by GSEA, STRING database, and Coexpedia online tool. Using TIMER and CIBERSORT method, the relationship between immune infiltrate and HMGA1 was investigated. RESULTS: In HCC, HMGA1 had much higher transcriptional and proteomic expression than in corresponding paraneoplastic tissue. Patients with high HMGA1 expression had a poor prognosis and unpromising clinicopathological features. High HMGA1 expression was closely related to the cell cycle, tumorigenesis, substance metabolism, and immune processes by regulating complex signaling pathways. Notably, HMGA1 may be associated with TP53 mutational carcinogenesis. Moreover, increased HMGA1 expression may lead to an increase in immune infiltration and a decrease in tumor purity in HCC. CIBERSORT analysis elucidated that the amount of B cell naive, B cell memory, T cells gamma delta, macrophages M2, and mast cell resting decreased when HMGA1 expression was high, whereas T cells follicular helper, macrophages M0, and Dendritic cells resting increased. CONCLUSION: In conclusions, HMGA1 is a potent prognostic biomarker and a sign of immune infiltration in HCC, which may be a potential immunotherapy target for HCC.

Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells.

BACKGROUND: It has been reported that atractylodin has a potential antitumor effect. This study aimed to investigate the effects of atractylodin on Huh7 and Hccm hepatocellular carcinoma (HCC) cells and its molecular mechanism. METHODS: Huh7 and Hccm cells were cultured in vitro, and their viability was detected by CCK-8 assay and the half inhibitory concentration (IC50) was calculated. The cells were treated with different concentrations of atractylodin, and the migration and invasion ability of cells was detected by scratch assay and Transwell assay. The cell cycle change and apoptosis rate were detected by flow cytometry. IlluminaHiSeq4000 platform was used for transcriptome sequencing, and the results were analyzed for gene differential expression, gene function, and signal pathway enrichment. Morphological changes of cells were detected by transmission electron microscopy, reactive oxygen species (ROS) levels were detected by DCFH-DA probe, and the expressions of ferroptosis related proteins GPX4, ACSL4, FTL, and TFR1 were detected by Western blot. RESULTS: The results showed that atractylodin could inhibit the proliferation, migration, and invasion of Huh7 and Hccm cells, regulate the cell cycle, and induce cell apoptosis and G1 phase cell cycle arrest. In addition, it could significantly induce the increase of intracellular ROS levels, decrease the expression of GPX4 and FTL proteins, and up-regulate the expression of ACSL4 and TFR1 proteins. CONCLUSIONS: Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, our results suggest that atractylodin may induce ferroptosis in HCC cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins.

Screening potential prognostic biomarkers for portal vein emboli in patients with hepatocellular carcinoma.

BACKGROUND: The formation of portal vein tumor thrombus (PVTT) is closely related to the prognosis of patients with hepatocellular carcinoma (HCC). However, the mechanisms by which PVTTs form and the biomarkers involved are still little understood. METHODS: The Genome Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain transcriptome data from normal tissue, HCC tissue, primary tumors (PTs) of HCC, and paired PVTT tissue. Differentially expressed genes (DEGs) in PTs and PVTTs were analyzed. The differentially expressed immune genes were further investigated in terms of their prognostic significance, immune infiltration, function. Finally, we explored the relationship between risk scores and drug sensitivity based on the R package. RESULTS: In the two datasets, there were 458 DEGs identified in the PT and PVTT tissues, of which, 58 were immune-related genes. The differentially expressed immune genes may promote the progression of PVTT by participating in the regulation of non-cellular components such as the extracellular matrix, inflammatory factors, and chemokines. Furthermore, the immune genes KDR, AKT3, FCGR2B, KIAA1429, and TPT1 were correlated with the prognosis of HCC in patients with PVTT. Using this data, a model was constructed to predict the prognosis of patients, thus allowing for the identification of high- and low-risk patients. CONCLUSIONS: This study demonstrated that immune-related genes may be involved in the regulation of the extracellular matrix and acellular components, and subsequently, in the formation of PVTT. These five genes KDR, AKT3, FCGR2B, KIAA1429, and TPT1 may be potential prognostic biomarkers and treatment targets for HCC patients with PVTT.

Correlation analysis of tumor mutation burden of hepatocellular carcinoma based on data mining.

BACKGROUND: The aim of this study was to determine the relationship between tumor mutation burden (TMB) and prognosis of patients with hepatocellular carcinoma (HCC), and to explore the differential expression of genes in HCC by TMB and the relationship between immune cells, TMB, and HCC. METHODS: Somatic variation data, gene transcriptional expression data and clinical information of patients with HCC were obtained from cancer genome map (TCGA) database. Analyze the characteristics of the gene mutation data of the sample, divide the high and low TMB groups and draw the survival curve at the same time, carry on the difference analysis to the gene of TMB, further carry on the univariate Cox regression analysis and Lasso regression analysis and construct the clinical model. Download the dataset GSE14520, from the Gene Expression Omnibus (GEO) database to verify the genes of the prognostic model. The differential genes were analyzed by gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes by (KEGG) enrichment analysis. Then the relative abundance of 22 immune cell types in HCC and normal control samples was calculated. Finally, the correlation between the scores of immune cells and Risk model was analyzed. RESULTS: Tumor protein p53 (TP53), catenin1 (CTNNB1), titin (TTN), mucin 16 (MUC16), and albumin (ALB) are the most common top 5 mutations in HCC. The prognosis of high level TMB group is worse than that of low TMB group. A total of 122 differentially expressed genes were screened by differential analysis of TMB genes. SQSTM1, ME1, BAMBI and PTTG1 are independent risk factors for poor prognosis of HCC. GO and KEGG analysis showed that the differential genes were mainly in extracellular matrix and immune response. There were significant differences in the distribution of Macrophages M0 and T cells CD4 native cells between HCC and normal tissues, which were correlated with the differential genes of TMB and correlated with prognosis. CONCLUSIONS: There is a negative correlation between TMB and the prognosis of patients with HCC. TMB has an effect on the differential expression of genes in HCC cells and the distribution of immune cells in tumor tissues.

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models.

BACKGROUND: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. METHODS: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. RESULTS: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. CONCLUSIONS: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

Laparoscopic versus open hepatectomy for hepatocellular carcinoma with cirrhosis: a single-center propensity score matching analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) remains controversial due to limited research. This study analyzed the oncology prognosis of patients who received LH treatment for HCC compared with conventional open hepatectomy (OH). METHODS: We conducted a retrospective analysis of patients with cirrhosis who underwent hepatectomy for HCC between 2012 and 2018. Patients were divided into LH and OH groups, and the oncology outcomes were compared before and after 1:1 propensity score matching (PSM). RESULTS: A total of 403 patients with HCC cirrhosis who received LH (n=112) and OH (n=291) were enrolled. After PSM, 106 pairs of patients were matched. Compared with OH before and after PSM, there was no significant difference in overall survival (OS) and relapse-free survival (RFS) between the two groups. Tumor stage, Child-Pugh classification, venous tumor thrombus, tumor size ≥5 cm, and microvascular invasion (MVI) were independent risk factors for postoperative OS in HCC patients with cirrhosis. Tumor size ≥5 cm and MVI were independent risk factors for RFS. CONCLUSIONS: Patients with HCC who underwent LH had a similar OS and RFS compared with those who received traditional open surgery. Therefore, LH can be used as a safe and feasible treatment for patients with HCC.

Molecular mechanism of CK19 involved in the regulation of postoperative recurrence of HBV-associated primary hepatocellular carcinoma in Guangxi.

BACKGROUND: Cytokeratin 19 (CK19/KRT19) is a marker of biliary epithelial cells and hepatic progenitor cells, which can be expressed in some hepatocellular carcinoma (HCC). However, its role in the occurrence, development, and recurrence of hepatitis B virus (HBV)-associated HCC remains to be clarified. This study is to analyze the relationship between the expression of CK19 protein and clinicopathological factors, as well as the effect of positive CK19 expression on the prognosis of HCC patients. METHODS: Small interfering RNA (siRNA) transfection was used to silence CK19 in MHCC-97H and Hep-3B. Real time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and flow cytometry were used to detect the effects of CK19 silencing on cell function. High-throughput sequencing was used to explore the potential molecular mechanism of CK19 positive expression of HCC. RESULTS: In 24 patients with HCC, CK19 was only expressed in cancer tissues, regardless of primary or recurrent tumors, and the positive expression rate of recurrent tumors was higher than that of primary tumors. The HCC participants with positive primary CK19 expression had a shorter tumor-free survival time. Silencing of the CK19 gene in MHCC-97H and Hep-3B attenuated the migration and invasion ability of MHCC-97H, increased the G2 phase cell content of MHCC-97H and Hep-3B, and increased the proportion of apoptosis. High-throughput sequencing results suggested that changes in the function of the cell cycle regulating genes, drug, and carcinogenic metabolism might be the potential pathways of CK19 in regulating the biological behavior of HCC. CONCLUSIONS: Among HBV-related recurrent HCC, the positive rate of CK19 expression in recurrent HCC tumors was higher, and the tumor-free survival time of HCC patients with positive CK19 expression in primary HCC was shorter. After silencing of the CK19 gene, the migration and invasion ability of HCC cells were weakened, the content of G2-M cell cycle cells was increased, the invasion and migration of HCC cells were inhibited, and apoptosis was promoted. Changes in the function of the cell cycle regulating genes and the regulation of drug and carcinogenic metabolites-related pathways may be the pathways through which CK19 affects the biological behavior of HCC.

Prognostic value and potential molecular mechanism of the like-Sm gene family in early-stage pancreatic ductal adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the prognostic significance of like-Sm (LSM) genes in early pancreatic ductal adenocarcinoma (PDAC) and explore the potential molecular mechanism. The protein product of the LSM1 gene is also known as CASM and YJL124C, while that of the LSM4 gene is known as GRP and YER112W. METHODS: Data from 112 patients attached to the Whipple surgery were collected from the TCGA database of clinical characteristics and survival data. The Kaplan-Meier method and the multivariate Cox proportional risk regression model were used to analyze the impact of LSM genes on outcomes in these 112 patients. We performed gene-gene interaction (GGI) and protein-protein interaction (PPI) analysis to probe interactions between LSM family genes. Bioinformatics techniques were applied to study the potential early-stage molecular mechanisms of LSM genes. Previously, only a few studies have explored the role and potential mechanisms of LSM1 in pancreatic tumor transformation, revealing possible links to transforming growth factor-ß, altering the expression of MMP1, uPAR, and SerpinB5 to enhance invasion and metastasis in pancreatic cancer, and facilitating mRNA decapping and degradation. Gene set enrichment analysis (GSEA) also proved that LSM genes are associated with RNA splicing, RNA synthesis, and RNA decomposition, and they may indirectly cause carcinogenesis through other genes such as myc. RESULTS: The results showed that LSM1 (adjusted P=0.004) and LSM4 (adjusted P=0.034) were associated with the prognosis of patients with PDAC, and patients with high expression levels of LSM1 (adjusted HR =2.338) or LSM4 (adjusted HR =1.803) tended to experience bad outcomes. CONCLUSIONS: Our study revealed that LSM1 and LSM4 might be used as prognostic biomarkers in early PDAC.