A signature based on neutrophil extracellular trap-related genes for the assessment of prognosis, immunoinfiltration, mutation and therapeutic response in hepatocellular carcinoma.

BACKGROUND: Liver cancer is a highly lethal and aggressive form of cancer that poses a significant threat to patient survival. Within this category, liver hepatocellular carcinoma (LIHC) represents the most common subtype of liver cancer. Despite decades of research and treatment, the overall survival rate for LIHC has not significantly improved. Improved models are necessary to differentiate high-risk cases and predict possible treatment options for LIHC patients. Recent studies have identified a set of genes associated with neutrophil extracellular traps (NETs) that may contribute to tumor growth and metastasis; however, their prognostic value in LIHC has yet to be established. This study aims to construct a prognostic signature based on a set of NET-related genes (NRGs) for patients diagnosed with LIHC. METHODS: The transcriptomic data and clinical information concerning LIHC patients were procured from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium LIHC (ICLIHC) databases, respectively. To determine the NRG subtypes, the k-means algorithm was employed, along with consensus clustering. The aforementioned analysis aided the construction of a prognostic signature utilizing the last absolute shrinkage and selection operator Cox analysis. To validate the prognostic model, an external dataset, receiver operating characteristic curve, and principal component analysis were utilized. Moreover, the immune microenvironment and the proportion of immune cells between high- and low-risk cases were scrutinized by ESTIMATE and CIBERSORT algorithms. Finally, gene set enrichment analysis was executed to investigate the potential mechanism of NRGs in the pathogenesis and prognosis of LIHC. RESULTS: Two molecular subtypes of LIHC were identified based on the expression patterns of differentially expressed NRGs (DE-NRGs). The two subtypes demonstrated significant differences in survival rates and immune cell expression levels. The study results demonstrated the role of NRGs in antigen presentation, which led to the promotion of tumor immune escape. A risk model was developed and validated with strong overall survival prediction ability. The model, comprising 34 NRGs, showed a strong ability to predict prognosis. CONCLUSION: We built a dependable prognostic signature based on NRGs for LIHC. We identified that NRGs could have a significant interaction in LIHC's immune microenvironment and therapeutic response. This finding offers insight into the molecular mechanisms and targeted therapy for LIHC.

Drug resistance of hepatoma cells induced by ATP­binding cassette transporter G2 by reducing intracellular drug concentration.

The side effects and drug resistance during chemotherapy seriously affect the outcome of and may lead to the failure of chemotherapy for patients with hepatoma. The aim of the present study was to investigate the association between the expression of ATP-binding cassette transporter G2 (ABCG2) in hepatoma cells and the drug resistance of hepatoma. An MTT assay was used to determine the half-maximal inhibitory concentration (IC50) of Adriamycin (ADM) in hepatoma HepG2 cells after treatment with ADM for 24 h. An ADM-resistant hepatoma cell subline, HepG2/ADM, was generated from the HepG2 hepatoma cell line through a stepwise selection with ADM doses from 0.01 to 0.1 µg/ml. The HepG2/ABCG2 cell line, an ABCG2-overexpressing hepatoma cell line, was established by transfecting the ABCG2 gene into HepG2 cells. The MTT assay was then used to detect the IC50 of ADM in HepG2/ADM and HepG2/ABCG2 cells after treatment with ADM for 24 h and the resistance index was calculated. The apoptosis, cell cycle and ABCG2 protein expression levels in HepG2/ADM, HepG2/ABCG2 cells, HepG2/PCDNA3.1 and their parental HepG2 cells were detected by flow cytometry. In addition, flow cytometry was used to detect the efflux effect of HepG2/ADM and HepG2/ABCG2 cells after ADM treatment. ABCG2 mRNA expression in cells was detected by reverse transcription-quantitative PCR. After 3 months of ADM treatment, HepG2/ADM cells grew stably in the cell culture medium containing 0.1 µg/ml ADM and the cells were named HepG2/ADM cells. ABCG2 was overexpressed in HepG2/ABCG2 cells. The IC50 of ADM in HepG2, HepG2/PCDNA3.1, HepG2/ADM and HepG2/ABCG2 cells was 0.72±0.03, 0.74±0.01, 11.17±0.59 and 12.75±0.47 µg/ml, respectively. The cell apoptotic rate of HepG2/ADM and HepG2/ABCG2 cells was not significantly different compared with that of HepG2 and HepG2/PCDNA3.1 cells (P>0.05), but the G0/G1 phase population of the cell cycle decreased and the proliferation index increased significantly (P<0.05). The expression levels of ABCG2 gene and protein in HepG2/ADM and HepG2/ABCG2 cells were significantly higher than those in HepG2 and HepG2/PCDNA3.1 cells (P<0.01), but there was no significant difference between HepG2 and HepG2/PCDNA3.1 cells (P>0.05). The ADM efflux effect of HepG2/ADM and HepG2/ABCG2 cells was significantly higher than that of parental HepG2 and HepG2/PCDNA3.1 cells (P<0.05). Therefore, the present study demonstrated that ABCG2 expression is highly increased in drug-resistant hepatoma cells and that high expression of ABCG2 is involved in the drug resistance of hepatoma by reducing the intracellular drug concentration.

The Role of m6A Modification and m6A Regulators in Esophageal Cancer.

N6-methyladenosine (m6A) modification, the most prevalent RNA modification, is involved in all aspects of RNA metabolism, including RNA processing, nuclear export, stability, translation and degradation. Therefore, m6A modification can participate in various physiological functions, such as tissue development, heat shock response, DNA damage response, circadian clock control and even in carcinogenesis through regulating the expression or structure of the gene. The deposition, removal and recognition of m6A are carried out by methyltransferases, demethylases and m6A RNA binding proteins, respectively. Aberrant m6A modification and the dysregulation of m6A regulators play critical roles in the occurrence and development of various cancers. The pathogenesis of esophageal cancer (ESCA) remains unclear and the five-year survival rate of advanced ESCA patients is still dismal. Here, we systematically reviewed the recent studies of m6A modification and m6A regulators in ESCA and comprehensively analyzed the role and possible mechanism of m6A modification and m6A regulators in the occurrence, progression, remedy and prognosis of ESCA. Defining the effect of m6A modification and m6A regulators in ESCA might be helpful for determining the pathogenesis of ESCA and providing some ideas for an early diagnosis, individualized treatment and improved prognosis of ESCA patients.

Right costophrenic angle abscess due to Salmonella Dublin infection in combination with type 2 diabetes mellitus.

The main manifestations of type 2 diabetes mellitus are excessive drinking, polyphagia, polyuria and wasting or weight loss in a short period of time, but it is rare to have persistent fever of unknown origin as the main manifestation. This case report describes a 68-year-old male patient with type 2 diabetes mellitus presenting with unexplained fever with persistent exacerbation and a cystic lesion in the right costophrenic horn on abdominal computed tomography (CT). A cytoculture examination of the puncture fluid suggested that the infection was due to Salmonella Dublin. The patient was treated with drainage of the abscess in the right costophrenic angle area, which then healed successfully. These findings suggest that Salmonella Dublin infection should be considered when a patient with type 2 diabetes mellitus presents with an unexplained persistent fever. At the same time, CT-guided abscess puncture can be performed to improve the patient's symptoms, aid diagnosis and improve the quality of life.

Survival risk prediction model for patients with pT1-3 N0M0 esophageal squamous cell carcinoma after R0 esophagectomy with two-field lymphadenectomy for therapeutic purposes.

BACKGROUND: The overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1-3N0M0 ESCC. METHODS: Patients with pT1-3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially. RESULTS: This study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001). CONCLUSIONS: Several factors were associated with the survival of patients with pT1-3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy.

Correlates of Long-Term Survival of Patients with pN+ Esophageal Squamous Cell Carcinoma after Esophagectomy.

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. Patients with ESCC have poor long-term survival, especially those with lymphatic metastasis (pN + ESCC). In this retrospective study, we evaluated the correlates of long-term survival time of patients with pN + ESCC. A total of 453 patients with pN + ESCC who underwent surgical R0 resection between Jan 2008 and Sep 2011 were enrolled. The follow-up ended on December 2019. The clinical, pathological, inflammation-related factors and general survival data of these patients were analyzed using SPSS 22.0 software. The 1-, 3-, and 5-year overall survival (OS) rates were 73.7%, 34.6%, and 25.6%, respectively; the 1-, 3-, and 5-year disease-free survival (DFS) rates were 45.0%, 26.3%, and 20.4%, respectively. The median OS and DFS were 23 and 14 months, respectively. On multivariate analyses, gender, site of lesion, number of dissected lymph nodes, stage pTNM, adjuvant therapy, and neutrophil lymphocyte ratio were independent predictors of OS. Site of lesion, stage pTNM, and adjuvant therapy were independent predictors of DFS. Recursive partitioning analysis (RPA) scores of each patient were calculated based on the independent predictors of OS, and the patients were divided into 3 classes: low-risk, medium-risk, and high-risk. The OS, DFS, and local recurrence-free survival were significantly different among these three RPA classes (P < 0.001). Several factors showed an independent association with long-term postoperative survival of pN + ESCC patients after radical surgery. RPA scores can potentially be used to predict the prognosis of ESCC.

Postoperative Adjuvant Therapy for Patients with pN+ Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. However, patient survival time after surgery remains unsatisfactory, especially in those who are pN+. This retrospective study determined the value of postoperative adjuvant therapy for patients with pN+ ESCC. From Jan 2008 to Sep 2011, 453 pN+ ESCC patients who underwent R0 resection and survived for at least 1 month were retrospectively enrolled. All patients received surgery. Some patients received surgery alone (SA, n = 131), and others received postoperative chemotherapy (POCT, n = 222), radiotherapy (PORT, n = 57), or sequential chemoradiotherapy (POCRT, n = 43). The follow-up ended on 1 Dec 2019. The 5-year overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LR) were significantly worse in the SA group (15.2%, 13.1%, and 71.6%, all p < 0.05) than in the POCT group (28.0%, 20.8%, and 66.5%), the PORT group (27.4%, 24.4%, and 46.9%), and the POCRT group (42.8%, 35.5%, and 43.0%). Furthermore, compared with the SA group, the median OS and DFS were significantly longer in the POCT, PORT, and POCRT groups (all p < 0.05). PORT and POCRT (but not POCT) also significantly reduced the LR (p < 0.01). Multivariate Cox analysis showed that each type of postoperative therapy was independently associated with improvements in OS, DFS, and LR. Postoperative adjuvant therapy-either POCT, PORT, or POCRT-significantly improved OS and DFS in patients with pN+ ESCC after R0 surgery. PORT and PORCT significantly reduced LR in these patients.

Risk factors for tumor recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma after esophagectomy.

OBJECTIVE: To analyze the factors contributing to recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Patients with pT3N0M0 thoracic ESCC who underwent esophagectomy from January 2008 to December 2012 were included retrospectively. The last date of follow-up was 1 December 2016. Multivariate proportional hazard Cox models were used to identify factors associated with total (i.e., any) recurrence (TR), locoregional recurrence (LR), and distant metastasis (DM). RESULTS: A total of 692 patients were included. The median follow-up was 53 months (range: 3-107). The 3- and 5-year TR, LR, and DM rates were 35.8% and 41.0%, 28.7% and 32.1%, and 16.8% and 21.1%, respectively. The Cox analyses showed that the tumor location, number of dissected lymph nodes, and postoperative therapies were significantly associated with LR. The subgroup analysis showed that postoperative therapies could significantly decrease LR in the mediastinum but not in the neck and upper abdomen regions. CONCLUSIONS: The recurrence rate of pT3N0M0 thoracic ESCC patients was high, especially for LR in the mediastinum. Postoperative therapies can significantly reduce the incidence of mediastinal recurrence.

Successful intraoperative management in patients with abdominal compartment syndrome induced by giant liposarcomas: Two case reports.

RATIONALE: Giant intra-abdominal liposarcomas weighing over 20 kg often increase the intra-abdominal pressure (IAP), which has severe effects on the cardiovascular and respiratory systems. Abdominal compartment syndrome is defined typically as the combination of a raised IAP of 20 mm Hg or higher and new onset of organ dysfunction or failure. The anesthetic management and perioperative management are very challenging. PATIENTS CONCERNS: We presented 2 patients with rare giant growing liposarcoma of the abdomen, weighing 21 kg and over 35 kg, respectively. Circulatory management was particularly difficult in the first case, while respiratory management and massive blood loss was very challenging in the second one. DIAGNOSIS: With a computed tomography scan and peritoneal-to-abdominal height ratio measurement, preoperatively the risk of developing intra-abdominal hypertension and abdominal compartment syndrome was recognized early in each patient. The inferior vena cava and right atrium of the first patient was compressed and malformed due to the uplifted diaphragm, while there was severe decreased lung volume and increased airway resistance, because of rare giant retroperitoneal liposarcomas in the second case. Histologic examination revealed dedifferentiated liposarcoma in both cases. INTERVENTIONS: Both of the patients underwent resection surgery with multiple monitoring; transesophageal echocardiography monitoring in the first case and pressure-controlled ventilation volume guaranteed mechanical ventilation mode in both cases. OUTCOMES: Intraoperatively and postoperatively no cardiopulmonary complications in both patients. The first patient was discharged without any complications on postoperative day 10, and the second patient underwent another surgery because of anastomotic leakage resulting from bowel resection. LESSONS: Multiple monitorings, in particular transesophageal echocardiography should be considered in patients with increased IAP due to a giant mass, while an appropriate lung protection ventilation strategy is crucial in these patients.

Application of CT images in the diagnosis of lung cancer based on finite mixed model.

Investigating the application of CT images when diagnosing lung cancer based on finite mixture model is the objective. METHOD: 120 clean healthy rats were taken as the research objects to establish lung cancer rat model and carry out lung CT image examination. After the successful CT image data preprocessing, the image is segmented by different methods, which include lung nodule segmentation on the basis of Adaptive Particle Swarm Optimization - Gaussian mixture model (APSO-GMM), lung nodule segmentation on the basis of Adaptive Particle Swarm Optimization - gamma mixture model (APSO-GaMM), lung nodule segmentation based on statistical information and self-selected mixed distribution model, and lung nodule segmentation based on neighborhood information and self-selected mixed distribution model. The segmentation effect is evaluated. RESULTS: Compared with the results of lung nodule segmentation based on statistical information and self-selected mixed distribution model, the Dice coefficient of lung nodule segmentation based on neighborhood information and self-selected mixed distribution model is higher, the relative final measurement accuracy is smaller, the segmentation is more accurate, but the running time is longer. Compared with APSO-GMM and APSO-GaMM, the dice value of self-selected mixed distribution model segmentation method is larger, and the final measurement accuracy is smaller. CONCLUSION: Among the five methods, the dice value of the self-selected mixed distribution model based on neighborhood information is the largest, and the relative accuracy of the final measurement is the smallest, indicating that the segmentation effect of the self-selected mixed distribution model based on neighborhood information is the best.

[Effect of perfusion CT scan on hepatic hemodynamic changes in rats with liver micrometastases].

BACKGROUND & OBJECTIVE: Hepatic metastases are common for patients with malignant tumors, especially for the gastrointestinal malignancies. Early diagnosis confers better prognosis. This study was designed to investigate the hepatic hemodynamic changes by multi-slice helical perfusion CT in rats with liver micrometastatases of Walker-256 tumor cells. METHODS: Liver micrometastatases were produced in 22 SD rats by injecting 2 x 10(7) Walker-256 cells into the spleens. The ten experimental control rats were injected with normal saline solution. Ten rats were randomized into empty self control group from the experimental group before injecting tumor cells, which were studied by CT perfusion technique before being injected tumor cells. The time-density curves of the aorta, portal vein, and liver were used to calculate liver perfusion parameters by gradient method designed for the dual blood supply. These liver perfusion parameters were hepatic arterial perfusion (HAP), portal vein perfusion (PVP), hepatic perfusion index (HPI) and total hepatic blood flow. All the parameters were compared between the groups. H&E staining method was used to confirm the micrometastases pathologically. RESULTS: In the experimental group, 19 rats were found with micrometastases, of which the diameter was 0.5 mm to 6.6 mm. HAP was (97.67+/-31.42) ml x min(-1) x (100 ml) (-1) in metastasis group, and (43.35+/-17.39)ml x min(-1) x (100 ml) (-1) in control group, and (40.77+/-18.91) ml x min(-1) x (100 ml) (-1) in empty self control group. PVP was (295.49+/-61.85) ml x min(-1) x (100 ml) (-1) in metastasis group, and (385.7+/-71.25) ml x min(-1) x (100 ml) (-1) in control group, and (362.73+/-78.56) ml x min(-1) x (100 ml) (-1) in empty self control group, It was found that the HAP was higher in the rats with micrometastases than in those of the empty control group and also those of control group (F=47.84, P<0.000,1). While the PVP was lower in the rats with micrometastases than in those of the two control groups (F=14.10, P<0.000,1). For the total hepatic blood flow, no significant difference was found among the three groups (F=1.39, P=0.255). CONCLUSION: Higher HAP and lower PVP was noted in the rats with micrometastases. Perfusion CT technique can be used to evaluate the hepatic hemodynamic changes and thus has a potential clinical value for early diagnosis of liver micrometastases.