A Lactic Acid Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironmental Status in Patients with Hepatocellular Carcinoma.

This study aims to build a prognostic model based on lactic acid metabolism-related genes (LMRGs) to predict survival outcomes and tumor microenvironment status of Hepatocellular carcinoma (HCC) patients. The model was used to calculate riskscores of clinical samples. Survival analysis and Cox regression analysis were conducted to verify the independence and reliability of the riskscore to determine its clinical significance in prognosis evaluation of HCC. Additionally, we conducted a comprehensive analysis of tumor mutation burden (TMB), immune cell infiltration, and gene set molecular function in the high- and low-risk groups. We obtained 134 LMRGs mainly involved in cellular calcium homeostasis and calcium signaling pathways. The LMRGs in the risk assessment model included PFKFB4, SLC16A3, ADRA2B, SLC22A1, QRFPR, and PROK1. This study discovered much shorter overall survival and median survival time of patients with higher riskscores when compared to those with lower riskscores. It was indicated that for independent prediction of patients' prognosis, the riskscore had a significant clinical value. A remarkable difference was also found regarding TMB between the two groups. Finally, cell experiments demonstrated that the knockout of PFKFB4 and SLC16A3 genes suppressed lactate. Our research demonstrated that the riskscore, established based on LMRGs, is a promising biomarker.

ETV4 facilitates proliferation, migration, and invasion of liver cancer by mediating TGF-ß signal transduction through activation of B3GNT3.

BACKGROUND: Metastasis of liver cancer (LC) is the main cause of its high mortality. ETV4 is a critical regulatory factor in promoting LC progression, but the mechanism that ETV4 impacts LC proliferation, migration, and invasion is poorly understood. OBJECTIVE: Investigation of the molecular mechanism of LC metastasis is conducive to developing effective drugs that prevent LC metastasis. METHODS: Expression of ETV4 and its target gene B3GNT3 in LC tissue was analyzed by bioinformatics, and the result was further verified in LC cells by qRT-PCR. In vitro cellular assays evaluated the impact of ETV4 on the proliferation, migration, and invasion of LC cells. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assay were conducted to analyze the interaction between B3GNT3 and ETV4. SB525334 suppressor was used to treat and access the activation of ETV4 on the TGF-ß pathway. RESULTS: We discovered that ETV4 and B3GNT3 were evidently up-regulated in LC, and high expression of ETV4 was coupled to the increase of proliferation, migration, and invasion of LC cells and epithelial-mesenchymal transition ability. Besides, ETV4 could bind to the B3GNT3 promoter and activate its transcription. Knockdown of B3GNT3 could prominently suppress the effect of up-regulated ETV4 on LC cells. Meanwhile, ETV4 could activate the TGF-ß signaling pathway via B3GNT3, while SB525334 treatment notably repressed the functions of ETV4. CONCLUSION: ETV4 emerges as a driven oncogene in LC, and the ETV4/B3GNT3-TGF-ß pathway promotes proliferation, migration, invasion, and epithelial-mesenchymal transition progress of LC. Inhibition of the pathway may provide an underlying method for the prevention and treatment of LC metastasis.

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and the mortality rate continues to rise each year. SMARCA4 expression has been associated with poor prognosis in various types of cancer; however, the specific mechanism of action of SMARCA4 in HCC needs to be fully elucidated. AIM: To explore the specific mechanism of action of SMARCA4 in HCC. METHODS: Herein, the expression level of SMARCA4 as well as its association with HCC prognosis were evaluated using transcriptome profiling and clinical data of 18 different types of cancer collected from The Cancer Genome Atlas database. Furthermore, SMARCA4-high and -low groups were identified. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the function of SMARCA4, followed by construction of a SMARCA4-specific competing endogenous RNA (ceRNA) network using starBase database. The role of SMARCA4 in immunotherapy and its association with immune cells were assessed using correlation analysis. RESULTS: It was observed that SMARCA4 was overexpressed and negatively correlated with prognosis in HCC. Further, SMARCA4 expression was positively associated with tumor mutational burden, microsatellite stability, and immunotherapy efficacy. The SNHG3/THUMP3-AS1-miR-139-5p-SMARCA4 ceRNA network was established and could be assumed to serve as a stimulatory mechanism in HCC. CONCLUSION: The findings of this study demonstrated that SMARCA4 plays a significant role in progression and immune infiltration in HCC. Moreover, a ceRNA network was detected, which was found to be correlated with poor prognosis in HCC. The findings of this study could contribute towards the identification of predictive markers for immunotherapy and a novel mechanism of action for HCC treatment.

Delineating Molecular Subtypes through Gene Set Variation Analysis Confers Therapeutic and Prognostic Capability in Gastric Cancer.

To claim the features of nontumor tissue in gastric cancer patients, especially in those who have undergone gastrectomy, and to identify the molecular subtypes, we collected the immunogenic and hallmark gene sets from gene set enrichment analysis. The activity changes of these gene sets between tumor (375) and nontumor (32) tissues acquired from the Cancer Genome Atlas (TCGA-STAD) were calculated, and the novel molecular subtypes were delineated. Subsequently, prognostic gene sets were determined using least absolute shrinkage and selection operator (lasso) regression prognostic method. In addition, functional analysis was conducted. Totally, three subtypes were constructed in the present study, and there were differences in survival among three groups. Functional analysis showed genes from normal gene set were related to cell adhesion, and genes from tumor gene set were associated with focal adhesion, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and VEGF signaling pathway. Our study created lasting value beyond molecular subtypes and underscored the significance of normal tissues in gastric cancer development, which drawn a novel prognostic model for gastric treatment.

Prognostic value of immune-related lncRNA pairs in patients with bladder cancer.

BACKGROUND: The characteristics of immune-related long non-coding ribonucleic acids (ir-lncRNAs), regardless of their specific levels, have important implications for the prognosis of patients with bladder cancer. METHODS: Based on The Cancer Genome Atlas database, original transcript data were analyzed. The ir-lncRNAs were obtained using a coexpression method, and their differentially expressed pairs (DE-ir-lncRNAs) were identified by univariate analysis. The lncRNA pairs were verified using a Lasso regression test. Thereafter, receiver operating characteristic curves were generated, and an optimal risk model was established. The clinical value of the model was verified through the analysis of patient survival rates, clinicopathological characteristics, presence of tumor-infiltrating immune cells, and chemotherapy efficacy evaluation. RESULTS: In total, 49 pairs of DE-ir-lncRNAs were identified, of which 21 were included in the Cox regression model. A risk regression model was established on the premise of not involving the specific expression value of the transcripts. CONCLUSIONS: The method and model used in this study have important clinical predictive value for bladder cancer and other malignant tumors.

Comparison of the effects and prognosis of concurrent and staged resections for the treatment of resectable colorectal cancer liver metastasis.

OBJECTIVE: To compare the effects and prognosis of concurrent and staged resections for the treatment of resectable colorectal cancer liver metastasis (CRLM). METHODS: A prospective study was conducted on 118 patients with CRLM. The 59 cases in the observation group received concurrent resections, while the 59 cases in the control group received staged resections. The operation time, intraoperative blood loss, length of hospital stay, hospital cost, postoperative complications, 5-year survival rate and 3-year progression-free survival rate were recorded for all patients. Factors that affect the prognosis of CRLM patients were analyzed. RESULTS: The length of hospital stay, operation time, intraoperative blood loss, hospital cost were significantly lower in the observation group than in the control group (P<0.001). The two groups were equivalent with respect to postoperative complications, 5-year survival rate and 3-year progression-free survival rate (P>0.05). Independent risk factors affecting the prognosis of CRLM included the number of liver metastasis, whether resection is feasible after recurrence, and RAS genotype (P<0.05). CONCLUSION: Compared to staged resection for CRLM, concurrent resection has shorter operation time, less blood loss, and shorter length of hospital stay, while postoperative complications, long-term efficacy and survival benefits are comparable. Furthermore, the study has found that the number of liver metastasis, whether or not resection is feasible after recurrence, and RAS genotype are risk factors affecting the prognosis of CRLM.

Bedside ultrasonography for acute appendicitis: An updated diagnostic meta-analysis.

BACKGROUND: Bedside ultrasonography is a promising tool for identification of acute appendicitis. We assessed the accuracy and clinical value of bedside ultrasonography for diagnosis of acute appendicitis in the emergency department. METHODS: Pubmed, Embase and Cochrane Library were searched from inception to November 2018. The diagnostic accuracy of bedside ultrasonography was compared with that of surgery and/or CT scan, which was used as reference standard. Pooled summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) from each included study were estimated using bivariate logistic regression model. Inter-study heterogeneity was examined using I2 statistic. Meta-regression was performed to further investigate the source of heterogeneity. Deeks's funnel plot was used to test publication bias. RESULTS: Our search yielded 5394 citations, of which 27 satisfied the inclusion criteria. Bivariate analysis yielded a mean sensitivity of 90% (95% CI 82%-0.95%) and specificity of 95% (95% CI 89%-98%). The area under the receiver operating characteristic curve was 0.97 (95% CI 0.95-0.98). There was significant inter-study heterogeneity (I2 = 96%, 95% CI 94%-99%). Meta-regression analysis suggested that study region and patient sample size could attribute to the heterogeneity. Deeks's funnel plot did not indicate the existence of publication bias (P = 0.15). CONCLUSION: Bedside ultrasonography, a radiation-free and noninvasive modality, provides superior diagnostic performance in the diagnosis of acute appendicitis, but its value in different abdominal emergencies warrants further development and research.

Endometriosis of the duplex appendix: A case report and review of the literature.

BACKGROUND: Duplication of the appendix is an infrequent congenital malformation with a complex classification. The horseshoe appendix is a subtype of the duplex appendix and is rarely reported in the literature. Endometriosis is a common gynecological disease that rarely occurs in the appendix. Moreover, horseshoe appendix combined with endometriosis has not been previously reported. CASE SUMMARY: Here, we describe a 44-year-old woman who was admitted with a 1-d history of migratory lower right quadrant pain. Physical examination was consistent with the signs of acute appendicitis. The patient underwent an emergency exploratory laparotomy. The distal tip of the appendix was in contact with the cecum by another base, or "horseshoe appendix". In addition, a small intestinal mass and an ovarian mass were identified. Subsequently, appendectomy, partial resection of the small intestine, and right oophorectomy were successively performed. The histopathology confirmed the diagnosis of acute inflammation of the duplex appendix with endometriosis, small intestine endometriosis, and ovarian endometriosis. CONCLUSION: Surgeons need to be aware of the possibility of the duplex appendix when performing an appendectomy, and this study emphasizes the importance of exploring the entire abdomen.