Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma.

Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Anti-herpes simplex virus activities of bioactive extracts from Antrodia camphorata mycelia.

BACKGROUND: Antrodia camphorata, a traditional Chinese medicine, is widely used in the treatment of liver diseases and cancers. Anti-inflammatory properties have also been described. HSV infection represents one of the most serious public health concerns globally because of its devastating impact. Searching for new antiviral agents, especially those with different mechanisms of action, is a crucial goal and there is an unmet need for alternative and complementary therapy against HSV infection. In this study, anti-herpes screening was performed with extracts from A. camphorata mycelia. METHODS: MTT assay, fractional inhibitory concentration index and median-effect principle were used to evaluate antiviral activity and to calculate drug combination effect. RESULTS: Crude ethanol extracts and isolated constituents showed inhibition of HSV replication at a very low concentration. Fraction A and antrodin A showed viral inhibitory effect with reduction of viral cell-to-cell spread. In addition, neither fraction A nor antrodin A showed interaction in combination with acyclovir. CONCLUSIONS: A. camphorata mycelia and antrodin A might have potential use as anti-HSV agents and are promising candidates for future antiviral drug design.

[Comparison among three reconstruction techniques after distal radical gastrectomy].

OBJECTIVE: To compare surgical efficacy after three different reconstruction techniques after radical resection of distal gastric cancer. METHODS: Clinical data of 169 cases of distal gastric cancer operated in our hospital from 2007 to 2010 were retrospectively analyzed. The reconstruction techniques included Billroth I (anastomosis (n=60), Billroth II (anastomosis (n=41), and Roux-en-Y anastomosis (n=68). Efficacy among 3 groups was compared. Specific symptoms scale was used to evaluate the quality of life in three methods after three months. RESULTS: Compared to Billroth I(anastomosis and Billroth II (anastomosis, Roux-en-Y anastomosis had longer operative time [(266.3±70.4) min vs. (196.2±54.3) min, and (228.5±67.7) min], more blood loss [(220.9±67.6) ml vs. (170.5±61.5) ml and (188.5±76.7) ml], and shorter time to gastric tube removal [(2.6±1.5) d vs. (3.1±1.3) d and (3.6±1.2) d], milder postoperative reflux and heartburn sensation(specific symptoms scale, 1.8±0.4 vs. 1.9±0.6 and 2.6±0.4, P<0.05). CONCLUSIONS: Although Roux-en-Y anastomosis is not consistent with physiological route and the procedure is more complex to perform, it can effectively prevent reflux complications. Roux-en-Y anastomosis is a better reconstruction technique after radical resection of distal gastric cancer.

[Analysis for myeloperoxidase genetic polymorphism in gastric cancer].

OBJECTIVE: To investigate the association of myeloperoxidase(MPO) genetic polymorphism and gastric cancer. METHODS: A case-control study was performed including 62 patients with gastric cancer and 61 healthy controls. Peripheral blood was collected for genetic analysis of MPO-463. RESULTS: There were no significant differences in gender, age, and smoking between the two groups(P>0.05). However, the two groups differed in drinking, family history of gastric cancer, and Helicobacter pylori(HP) infection(P<0.05). The frequencies of MPO-463GG, GA and AA were 87.1%, 11.3% and 1.6%in the study group, and were 72.1%, 23.0%, and 4.9% in the control group, respectively. Carriers of MPO-463 GA or AA had a significantly higher risk of gastric cancer than those of MPO-463 GG(χ(2)=4.253, P<0.05, OR=0.383, 95% CI: 0.151-0.972). Carriers of G allele had a significantly lower risk of gastric cancer compared to carriers of A allele(χ(2)=4.935, P<0.05, OR=0.399, 95% CI: 0.174-0.916). CONCLUSION: MPO-463 G/A polymorphism is associated with gastric cancer with A being a protective gene.