Novel risk model based on angiogenesis-related lncRNAs for prognosis prediction of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.

Association between the non-HDL-cholesterol to HDL-cholesterol ratio and non-alcoholic fatty liver disease in Chinese children and adolescents: a large single-center cross-sectional study.

BACKGROUND: The non-HDL-cholesterol to HDL-cholesterol (NHDLC/HDLC) ratio is closely related to a variety of dyslipidemia-related diseases. This study examined the relationship between the NHDLC/HDLC ratio and non-alcoholic fatty liver (NAFLD) in children and adolescents. METHODS: This cross-sectional survey included a total of 7759 eligible Chinese children and adolescents (5692 boys and 2067 girls) who received routine medical examinations. The anthropometric and laboratory data of the subjects were collected. NAFLD was diagnosed by liver ultrasonography. Binary logistic regression analysis was performed on the NHDLC/HDLC ratio, NHDLC, HDLC and NAFLD. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic significance of the above parameters for NAFLD. RESULTS: The total prevalence of NAFLD was 4.36%, and the prevalence in boys was higher than that in girls (5.61% vs. 1.9%, P < 0.001). The prevalence of NAFLD was positively correlated with the NHDLC/HDLC ratio (P < 0.001). The binary logistic regression analysis demonstrated that the OR was 8.61 (95% CI, 5.90-12.57, P < 0.001) in tertile 3 (highest NHDLC/HDLC ratio) compared with tertile 1 (lowest NHDLC/HDLC ratio). After adjustment for age, sex, body mass index (BMI), alanine aminotransferase (ALT), uric acid (UA), total bilirubin (TB), fasting plasma glucose (FPG) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the OR for tertile 3 (OR = 1.83, 95% CI, 1.04-3.22, P = 0.035) was still significantly higher than that of tertile 1. The area under the curve (AUC) of the NHDLC/HDLC ratio of boys was 0.787, which was significantly greater than NHDLC and HDLC (0.719 and 0.726, P < 0.001). For girls, the AUC of the NHDLC/HDLC ratio was 0.763, which was also significantly greater than NHDLC (0.661, P < 0.001). The cutoff point of the NHDLC/HDLC ratio was 2.475 in boys and 2.695 in girls. In addition, the AUC of the NHDLC/HDLC ratio was 0.761 in subjects with normal ALT levels (ALT ≤40 U/L), which was significantly higher than NHDLC (0.680, P < 0.001) and HDLC (0.724, P = 0.007). For subjects with elevated ALT levels (ALT > 40 U/L), the AUC of the NHDLC/HDLC ratio (0.746) was also significantly greater than NHDLC (0.646, P < 0.001). CONCLUSIONS: The NHDLC/HDLC ratio was positively correlated with NAFLD in Chinese children and adolescents. It may serve as an effective indicator to help identify NAFLD in children and adolescents.

Prognostic Value of Lymphovascular Invasion in Patients with Stage III Colorectal Cancer: A Retrospective Study.

BACKGROUND Lymph node metastasis and tumor progression depend on lymphovascular invasion (LVI). This study aimed to investigate the prognostic role of LVI in patients with stage III colorectal cancer (CRC) and to develop a prognostic nomogram. MATERIAL AND METHODS A retrospective study included 437 patients with stage III CRC. The impact of LVI on overall survival (OS) was analyzed with the Kaplan-Meier method and Cox regression model. A nomogram was constructed, and its predictive accuracy was evaluated using the concordance index (C-index) and the calibration plot. RESULTS LVI was found in 19.7% of cases of stage III CRCs and was significantly correlated with high tumor grade (poor differentiation) and advanced tumor stage (all P<0.05). Patients age, a family history of cancer in a first-degree relative, pre-treatment levels of carcinoembryonic antigen (CEA), prognostic nutritional index (PNI), histological tumor grade, tumor-node-metastasis (TNM) stage, and LVI were independent prognostic indicators (all P<0.05). Compared with the LVI(-) group, patients in the LVI(+) group showed a 1.748-fold increased risk of death (P=0.004) and a significantly reduced OS rate (P<0.001). In the prognostic nomogram, the C-index was significantly increased with LVI compared with the TNM stage alone (0.742 vs. 0.593; P<0.001). Calibration plots showed good fitness of the nomogram for prediction of survival. Comparison of the nomograms with and without LVI showed that inclusion of LVI improved the C-index from 0.715 to 0.742. CONCLUSIONS LVI was an indicator of more aggressive biological behavior and poor prognosis in patients with stage III CRC.

A novel prognostic signature based on immunogenic cell death score predicts outcomes and response to transcatheter arterial chemoembolization and immunotherapy in hepatocellular carcinoma.

PURPOSE: The phenomenon of immunogenic cell death (ICD) is intricately linked to numerous antitumor treatments and exerts a profound regulatory function in the tumor immune microenvironment (TIME). We aimed to establish a prognostic signature from the ICD-related biomarkers to differentiate the TIME in hepatocellular carcinoma and predict diverse outcomes for patients with liver cancer. METHODS: ICD score-related genes (ICDSGs) were identified using the weighted gene co-expression network analysis (WGCNA). The ICD score-related signature (ICDSsig) was established by applying LASSO and Cox regression. Model precision was verified using the external datasets. We used independent prognostic variables in clinicopathologic factors to develop a nomogram. Further, clinical characteristics, immune and molecular landscapes, the responses of transcatheter arterial chemoembolization (TACE) and immunotherapy, and chemotherapy sensitivity were analyzed for high- and low-risk patients. RESULTS: ICD score-calculated using the single-sample gene set enrichment analysis (ssGSEA)-displayed strong associations with the TIME in HCC. We identified 34 ICDSGs after integrating the TCGA and GSE104580 datasets. Then, three novel ICDSGs (DNASE1L3, KLRB1, and LILRB1) were screened out to construct the ICDSsig; the prognostic signature performed well in the external databases. The high-risk patients had worse outcomes owing to their advanced pathological state, non-response of TACE, and immune-cold phenotype in the immune landscapes. The immune checkpoint genes, N6-methyladenosine-relevant genes, and microsatellite instability score were increased in the high-risk subgroup, thereby indicating a favorable sensitivity to immunotherapy. Common chemotherapy drugs were more effective in high-risk patients due to low half-maximal inhibitory concentration values. CONCLUSION: The ICDSsig can potentially predict outcomes and therapeutic responses for patients with liver cancer and may assist clinicians in designing individualized treatment strategies.

Accessory spleen originating from the intrinsic muscularis of the stomach misdiagnosed as gastrointestinal stromal tumor: a case report.

A 34-year-old man presented to our hospital with a 2-month history of repeated dull upper abdominal pain. Gastroscopy and endoscopic ultrasonography indicated a hemispherical mass at the junction of the greater curvature and the gastric fundus, with hypoechogenicity originating from the intrinsic muscular layer. He was diagnosed with a gastric body submucosal lesion and gastrointestinal stromal tumor, and underwent endoscopic full-thickness resection. However, postoperative pathological examination of the mass unexpectedly revealed heterotopic spleen tissue (accessory spleen). Intragastric ectopic spleen tissue originating from the intrinsic muscular layer of the stomach is a rare clinical condition, with no specific clinical symptoms. This finding is of great clinical significance for the identification of gastric submucosal tumors.

The Role of Xenobiotic Receptors on Hepatic Glycolipid Metabolism.

BACKGROUND: PXR (Pregnane X Receptor) and CAR (Constitutive Androstane Receptor) are termed as xenobiotic receptors, which are known as core factors in regulation of the transcription of metabolic enzymes and drug transporters. However, accumulating evidence has shown that PXR and CAR exert their effects on energy metabolism through the regulation of gluconeogenesis, lipogenesis and ß-oxidation. Therefore, in this review, we are trying to summary recent advances to show how xenobiotic receptors regulate energy metabolism. METHODS: A structured search of databases has been performed by using focused review topics. According to conceptual framework, the main idea of research literature was summarized and presented. RESULTS: For introduction of each receptor, the general introduction and the critical functions in hepatic glucose and lipid metabolism have been included. Recent important studies have shown that CAR acts as a negative regulator of lipogenesis, gluconeogenesis and ß -oxidation. PXR activation induces lipogenesis, inhibits gluconeogenesis and inhabits ß-oxidation. CONCLUSION: In this review, the importance of xenobiotic receptors in hepatic glucose and lipid metabolism has been confirmed. Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome, including obesity and diabetes. However, further research is required to promote the clinical application of this new energy metabolism function of xenobiotic receptors.

High Rab11-FIP4 expression predicts poor prognosis and exhibits tumor promotion in pancreatic cancer.

Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4 ) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data. Rab11-FIP4 expression in PC tissues increased significantly more than that of adjacent non-cancerous tissues (P=0.0001). Overexpression of Rab11-FIP4 in the PC tissues was significantly related to tumor size (P=0.0001), histological grade (P=0.028), metastasis (P=0.001) and TNM stage (P=0.004) but not with age (P=0.832), gender (P=0.228) or tumor site (P=0.875). Kaplan-Meier survival analysis showed that overexpression of Rab11-FIP4 was significantly related to overall survival time (P=0.0036). In addition, Rab11-FIP4 in PANC-1 pancreatic cancer cells were successfully knocked-out using the CRISPR/Cas9 system. Rab11-FIP4 knockout in PANC-1 cells inhibited cell growth, invasion and metastasis, and arrested cell cycle progression, but did not alter apoptosis. Our findings suggest that overexpression of Rab11-FIP4 predicts poor clinical outcomes for pancreatic cancer and contributes to pancreatic tumor progression.

High expression of atonal homolog 8 predicts a poor clinical outcome in patients with colorectal cancer and contributes to tumor progression.

Hitherto, it has been identified that numerous basic-helix-loop-helix (bHLH) transcription factors play vital roles in tumor initiation and progression. Atonal homolog 8 (ATOH8) is a member of the bHLH family of transcription factors, which participates in embryogenesis and the development of various tissues. Several studies have demonstrated that ATOH8 is involved in the progression of malignancies; however, the effects of ATOH8 in colorectal cancer (CRC) remain unknown. The aim of the present study was to explore the expression and function of ATOH8 in CRC. The present study included 106 paired CRCs and peritumoral samples. The expression of ATOH8 was evaluated by immunohistochemistry, and the results were compared with the clinical outcomes of the patients. Furthermore, cell proliferation, cell cycle distribution, wound healing and cytotoxicity assays were performed in colon cancer cell line SW620. Immunohistochemical analyses revealed that the expression of ATOH8 in CRC tissues was significantly increased compared with the peritumoral tissues, and that the high expression of ATOH8 was associated with a high serum carcinoembryonic antigen (CEA) level and a worse overall survival. In vitro assays revealed that ATOH8 knockdown in colon cancer cells inhibited cell proliferation, induced cell cycle arrest at the S phase, and increased the percentage of apoptotic cells and sensitivity to 5-fluorouracil (5-FU). The present study suggests that ATOH8 promotes the progression of CRC and may potentially serve as a novel prognostic predictor and potential therapeutic target in CRC.

Application of the cell sheet technique in tissue engineering.

The development and application of the tissue engineering technique has shown a significant potential in regenerative medicine. However, the limitations of conventional tissue engineering methods (cell suspensions, scaffolds and/or growth factors) restrict its application in certain fields. The novel cell sheet technique can overcome such disadvantages. Cultured cells can be harvested as intact sheets without the use of proteolytic enzymes, such as trypsin or dispase, which can result in cell damage and loss of differentiated phenotypes. The cell sheet is a complete layer, which contains extracellular matrix, ion channel, growth factor receptors, nexin and other important cell surface proteins. Mesenchymal stem cells (MSCs), which have the potential for multiple differentiation, are promising candidate seed cells for tissue engineering. The MSC sheet technique may have potential in the fields of regenerative medicine and tissue engineering in general. Additionally, induced pluripotent stem cell and embryonic stem cell-derived cell sheets have been proposed for tissue regeneration. Currently, the application of cell sheet for tissue reconstruction includes: Direct recipient sites implantation, superposition of cell sheets to construct three-dimensional structure for implantation, or cell sheet combined with scaffolds. The present review discusses the progress in cell sheet techniques, particularly stem cell sheet techniques, in tissue engineering.