A prognostic signature of fatty acid metabolism-related genes for predicting survival of gastric cancer patients.

To analyze the expression profile of fatty acid metabolism (FAM)-related genes, identify a prognostic signature, and evaluate its clinical value for gastric cancer (GC) patients. The mRNA expression profiles of 493 FAM-related genes were obtained from TCGA database. Differentially expressed genes (DEGs) between cancer and non-cancer samples were identified, and their relationships with overall survival (OS) of GC patients were evaluated. A prognostic signature of FAM-related genes was identified by the LASSO regression model, and its predictive performance was tested by an independent external cohort. Ninety-three DEGs were identified, of which 44 were downregulated and 49 were upregulated. After optimizing risk characteristics, a prognostic signature of four FAM-related genes (ACBD5, AVPR1A, ELOVL4, and FAAH) were developed. All patients were divided into high-risk (>1.020) and low-risk groups (≤1.020) on the basis of the median risk score. Survival analysis indicated that high-risk patients had a shorter OS than low-risk patients (5-year OS rate, 26.3% vs. 45.0%, p < 0.001). The AUC values for the prediction of 3-year and 5-year OS were 0.664 and 0.624, respectively. In the GSE62254 data set, the 5-year OS rate of high-risk and low-risk patients were 44.7% versus 61.5%, respectively (p = 0.003). The AUC values were 0.632 and 0.627 at 3-year and 5-year prediction. The prognostic signature of FAM-related genes was an independent predictor of OS (hanzard ratio [HR] for TCGA cohort: 1.851, 95% confidence interval [CI]: 1.394-2.458, p < 0.001; HR for GSE62254: 1.549, 95% CI: 1.098-2.185, p = 0.013). The risk signature of four FAM-related genes was a valuable prognostic tool, and it might be helpful for clinical management and therapeutic decision of gastric cancer patients.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma.

OBJECTIVE: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. METHODS: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. RESULTS: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. CONCLUSIONS: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Identifying a Risk Signature of Methylation-Driven Genes as a Predictor of Survival Outcome for Colon Cancer Patients.

Aberrant expression of gene is driven by its promoter methylation and is the key molecular basis of carcinogenic processes. This study aimed at identifying a risk signature of methylation-driven (MD) genes and evaluating its prognostic value for colon cancer (CC) patients. The expression profiles of methylation and mRNA in CC samples were obtained from the TCGA database, and the MethylMix algorithm was used to identify MD genes. The relationships between their expression levels and overall survival (OS) of CC patients were analyzed, and a prognostic signature of MD genes was established. The risk score of gene signature was calculated, and the median was used to divide all patients into high (H) and low (L) risk groups. The prognostic value of gene signature was tested by the TCGA cohort and an independent validation cohort (GSE17538 dataset). In total, 69 MD genes were identified, and 7 were associated with OS of CC patients. Ultimately, 4 (TWIST1, LDOC1, EPHX3, and STC2) were screened out to establish a risk signature. The H-risk patients (>0.923) had a worse OS than L-risk patients (≤0.923) in both the TCGA (5-year cumulative survival: 52.9% vs 72.0%, P=0.005) and GSE17538 cohort (49.4% vs 69.3%, P=0.004). The AUC values of MD genes signature for the prediction of 3- and 5-year OS were 0.648 and 0.643 in the TCGA dataset and 0.634 and 0.624 in the GSE17538 dataset, respectively. The risk signature of four MD genes was identified as an independent predictor of OS for CC patients (HR for TCGA dataset: 2.071, 95% CI=1.196-3.586, P=0.009; HR for GSE17538 dataset: 2.021, 95% CI=1.290-3.166, P=0.002). The risk signature of four MD genes might be a useful prognostic tool and help doctors improve the clinical management of CC patients.

Construction and assessment of a joint prediction model and nomogram for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and all its risk factors are not yet known. It is important to identify valuable clinical indicators to predict the risk of CRC. Methods: A total of 227 participants, comprising 162 healthy adults and 65 patients diagnosed with CRC at Tianjin Hospital from January 2017 to March 2022, were included in this study. Electrochemiluminescence was adopted to test the expression levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CRC, and a joint prediction model was then constructed. A nomogram was prepared, and the model was later assessed using the receiver operating characteristic curve and calibration curve. Results: The univariate analysis showed that there were statistically significant differences between the two groups in terms of smoking (χ2=8.67), fecal occult blood (χ2=119.41), Helicobacter pylori (H. pylori) infection (χ2=30.87), a history of appendectomy (χ2=5.47), serum total bile acid levels (t=19.80), serum CEA levels (t=37.82), serum CA199 levels (t=6.82), and serum ferritin levels (t=54.31) (all P<0.05). The multiple logistic regression analysis showed that smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels were independent risk factors for CRC (all P<0.05). Based on the above findings, a joint prediction model was constructed, and the area under the receiver operator characteristic (ROC) curve of the model was 0.842. A nomogram and calibration curve was drawn, and the internal validation results indicated that the model had good diagnostic value. Conclusions: Smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels are independent risk factors for CRC, and the prediction model based on these factors had good predictive ability.

Enhancement of Medical Students' Performance and Motivation in Pathophysiology Courses: Shifting From Traditional Instruction to Blended Learning.

Blended learning is a learning approach that combines face-to-face classroom lectures and e-learning. It has grown rapidly to be commonly used in medical institutions, especially in the local medical universities where there is lack of qualified teachers and instructional materials. Massive open online courses (MOOCs) are the latest revolution in e-learning and provides learners with access to quality educational resources. Nevertheless, there is seldom reports concerning how to effectively integrate MOOCs into blended learning in local universities, as well as the evaluation of knowledge outcomes. In order to achieve this aim, a blended learning approach was carried out in teaching pathophysiology in Guilin Medical University. This blended learning model was based on combination of Chinese University MOOC with case based learning (CBL), as an alternative to conventional learning. The medical students in the 2017 and 2018 classes received the blended learning method, while the medical students in the 2015 class received the traditional classroom instruction. The results showed that students in the 2017 and 2018 performed significantly better than students in the 2015 class at mid-term exam and the final exam. Perception surveys also revealed that both students and teachers had positive attitude toward blended learning, and they shared similar viewpoints of blended learning. A large proportion of students and teachers believed that the blended learning enhanced students' motivation to learn independently, improved their time management skills, and allowed them to experience personalized learning. Also, most students and teachers recognized that Chinese University MOOC provided substantial educational resources suitable for their need. In addition, teachers indicated that the blended learning improved student learning quality, facilitated interaction between teachers and students, and helped them to establish a student-centered model in teaching pathophysiology. Overall, the blended learning method that combines Chinese University MOOC with CBL is effective in enhancing students' achievement and motivation in pathophysiology than the traditional learning method, and helps to strengthen the cultivation of talent in local medical universities.

MicroRNA-24 inhibits the proliferation, migration and invasion and enhances chemosensitivity of human gastric cancer by targeting DND1.

PURPOSE: Gastric cancer causes significant human mortality and is the fourth prevalent type of cancer across the globe. The gastric cancer treatment is hurdled by late diagnosis due to unavailability of biomarkers, lack of potent therapeutic targets and adverse effects of chemotherapy. Recent reports have indicated that miR-24 acts a tumor suppressor in different cancers. This study explored the role and therapeutic implications of miR-24 in gastric cancer. METHODS: Expression analysis was carried out in gastric cancer tissues and cell lines by qRT-PCR. Proliferation rate was monitored by WST-1 assay. Transwell assay was used to determine cell invasion and wound healing assay was used for cell migration. Protein expression analysis was carried out by western blot analysis. RESULTS: The results showed that miR-24 was significantly suppressed in gastric cancer tissues and cell lines. Overexpression of miR-24 in SNU-1 gastric cancer cells resulted in decline of proliferation rate in a time-dependent manner. In silico analysis together with the dual luciferase assay revealed RNA binding protein DND1 to be the target of miR-24. Expression analysis of DND1 was found to be significantly overexpressed in gastric cancer tissues and cell lines. Suppression of DND1 suppressed the proliferation of gastric cancer cells. Wound healing and transwell assay revealed that miR-24 overexpression also inhibited the migration and invasion and also enhanced the chemosensitivity of the SNU1 gastric cancer cells. CONCLUSION: Taken together, miR-24 may prove to be an important therapeutic target for the treatment of gastric cancer and warrants further studies.

MIG7 is involved in vasculogenic mimicry formation rendering invasion and metastasis in hepatocellular carcinoma.

Migration-inducing gene 7 (MIG7) is highly expressed and is implicated in multiple malignant tumors with vasculogenic mimicry (VM) which renders possible routes without the endothelium for invasion and metastasis. However, there are few reports in the literature describing the relationship between MIG7 expression and VM formation in hepatocellular carcinoma (HCC). In the present study, we found a significantly positive correlation between MIG7 expression and VM in 40 HCC specimens. Three-dimensional (3D) culture showed that VM formation in the HCC cell line MHCC-97H with high metastatic potential was enhanced to a greater extent than that of MHCC-97L and Huh-7 with low and non-metastatic potential. There was no VM formation in human normal hepatocyte line L-02. Moreover, MIG7 expression was higher in MHCC-97H than in MHCC-97L and Huh-7 cells and non-detectable in L-02 cells. MIG7 knockdown in MHCC-97H cells reduced VM formation, and weakened the invasive properties accompanying the enhanced cellular adhesion. Notably, there was no significant effect of endostatin (ES), a broad-spectrum angiogenesis inhibitor applied to clinical treatment, on both MIG7 expression and VM formation. Thus, the present study presents a causal link between MIG7 expression and VM formation in HCC, suggesting a potential treatment target for invasion and metastasis.

[MIG7 Regulates the Vasculogenic Mimicry Formation in Hepatocellular Carcinoma then Effects the Metastasis Potential of HCC].

OBJECTIVES: To investigate the expression of migration-inducing gene 7 (MIG7) in different HCC lines and its relationship with vasculogenic mimicry (VM) formation and metastatic potentiality. METHODS: Employing immunostaining to detect MIG7 protein expression and VM formation in 40 matched pairs of primary and metastatic HCC specimens from 40 patients, and investigating the correlation of VM formation with MIG7 protein expression. Detecting VM formation in HCC lines with different metastatic ability (MHCC-97H, MHCC-97L, Huh-7) and human normal hepatocyte line (L-02) through three-dimensional culture, and detecting MIG7 mRNA expression with RT-PCR, investigating the correlation of MIG7 protein expression with VM formation and HCC metastatic potentiality with Western blot assay; screening the HCC cell line with high MIG7 expression. RESULTS: In 40 matched pairs of HCC tissue, there was a significant positive correlation between MIG7 protein expression and VM formation ( rs=0.595, P<0.01). The capability of VM formation of MHCC-97H with high metastatic potentiality was stronger than that of MHCC-97L with low metastatic potentiality and Huh-7 with non-metastatic potentiality, and there was no VM formation in L-02. The result of RT-PCR and Western blot assay indicated the same. CONCLUSIONS: MIG7 expression in HCC tissue is high and correlated positively with VM formation. MIG7 expression in different HCC cell lines is coincident with theirs VM formation, invasion and metastasis. MIG7 is a potential target for inhibiting the invasion and metastasis of HCC.

Management of Advanced Hepatic Alveolar Echinococcosis: Report of 42 Cases.

Radical resection is the first choice for hepatic alveolar echinococcosis (HAE). However, many patients with advanced HAE have no chance to be treated with curative resection owing to the long clinical latency. This study aimed to evaluate the necessity of aggressive operations, like palliative resection and orthotopic liver transplantation (OLT), in the management of advanced HAE. A retrospective study analyzed 42 patients with advanced HAE treated with palliative resection (N = 15), palliative nonresective procedures (N = 13), OLT (N = 3), or albendazole therapy alone (N = 11). The patients' condition before treatments was comparable among all the four groups. The overall 1-year, 3-year, and 5-year survival rates of the 42 cases were 81.0%, 45.2%, and 23.8%, respectively. No event occurred to end the follow-up during the 5-year observation period except death. The survival time (median ± standard error) of the palliative resection group (3.6 ± 1.4 years) was longer than that of the palliative nonresective procedures group (1.5 ± 0.2) and the albendazole therapy-alone group (1.0 ± 0.4). The 5-year survival rates after palliative resection and liver transplantation were 40.0% and 66.7%, compared with only 7.7% and 9.1% after palliative nonresective procedures or albendazole therapy alone. Therefore, we concluded that aggressive treatment with a multimodality strategy could contribute to prolonged survival in patients with advanced HAE. Moreover, the prognosis of the patients who received albendazole therapy alone or palliative nonresective procedures is poor.

[Inhibitory effect of Mig-7 silencing by retrovirus-mediated shRNA on vasculogenic mimicry, invasion and metastasis of human hepatocellular carcinoma cells in vitro].

OBJECTIVE: To explore the inhibitory effect of migration-inducing gene 7 (Mig-7) gene silencing induced by retroviral-mediated small hairpin RNA (shRNA) on vasculogenic mimicry (VM), invasion and metastasis of human hepatocellular carcinoma (HCC) cells in vitro. METHODS: Two target sequences (Mig-7 shRNA-1 and Mig-7 shRNA-2) and one negative control sequence (Mig-7 shRNA-N) were synthesized. The recombinant retroviral vectors carrying Mig-7 shRNA were constructed, and HCC cell line MHCC-97H were transfected with Mig-7 shRNA-1, Mig-7 shRNA-2, Mig-7 shRNA-N, or the empty vector, or treated with 125 µg/mL recombinant human endostatin (ES). Mig-7 expression in the treated cells was detected using semi-quantitative PCR and Western blotting. The inhibitory effect of Mig-7 silencing on VM formation was investigated in a 3-dimensional cell culture system; the changes in cell adhesion, invasion and migration were assessed with intercellular adhesion assay, Transwell invasion assay and Transwell migration assay, respectively. RESULTS: The expression of Mig-7 at both mRNA and protein levels decreased significantly, VM formation, invasion and metastasis were suppressed, while intercellular adhesion increased significantly in MHCC-97H cells in Mig-7 shRNA-1 and Mig-7 shRNA-2 groups (P<0.05); such changes were not observed in cells transfected with Mig-7 shRNA-N or the empty vector, nor in cells treated with ES. CONCLUSIONS: Mig-7 silencing by retroviral-mediated shRNA significantly inhibits VM formation, invasion and metastasis and increases the intercellular adhesion of the HCC cells, while ES does not have such inhibitory effects.