Gene Expression Nebulas (GEN): a comprehensive data portal integrating transcriptomic profiles across multiple species at both bulk and single-cell levels.

Transcriptomic profiling is critical to uncovering functional elements from transcriptional and post-transcriptional aspects. Here, we present Gene Expression Nebulas (GEN, https://ngdc.cncb.ac.cn/gen/), an open-access data portal integrating transcriptomic profiles under various biological contexts. GEN features a curated collection of high-quality bulk and single-cell RNA sequencing datasets by using standardized data processing pipelines and a structured curation model. Currently, GEN houses a large number of gene expression profiles from 323 datasets (157 bulk and 166 single-cell), covering 50 500 samples and 15 540 169 cells across 30 species, which are further categorized into six biological contexts. Moreover, GEN integrates a full range of transcriptomic profiles on expression, RNA editing and alternative splicing for 10 bulk datasets, providing opportunities for users to conduct integrative analysis at both transcriptional and post-transcriptional levels. In addition, GEN provides abundant gene annotations based on value-added curation of transcriptomic profiles and delivers online services for data analysis and visualization. Collectively, GEN presents a comprehensive collection of transcriptomic profiles across multiple species, thus serving as a fundamental resource for better understanding genetic regulatory architecture and functional mechanisms from tissues to cells.

Synthesis, Performance, Mechanism: A Hyperbranched Phase Reverse Nano-Demulsifier for Condensate Emulsion.

Organic amine and nanosilica were combined to create a nano-demulsifier, which was employed in the oil-water separation process of a condensate emulsion. The nano-demulsifier has the structure of hyperbranched polymers and the skeleton structure of hyperbranched nanomaterials, and displays the demulsification impact of organic amine polymers as well as the synergistic effect of nanomaterials. This nano-demulsifier has the potential to drastically reduce the quantity of condensate demulsifiers utilized in the gathering station. The dehydration rate of the condensate lotion in the gas gathering station can reach more than 95% only at a concentration of 1.0 wt.%. Its application can significantly increase the separation efficiency of the condensate emulsion as well as the quality of condensate oil. It has a positive impact on cost reduction and efficiency in gas well production. The mechanism of action of the demulsifier was also studied, and the results show that the demulsifier is a phase reverse demulsifier.

miR-502-5p affects gastric cancer progression by targeting PD-L1.

BACKGROUND: Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. METHODS: Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. RESULTS: The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. CONCLUSIONS: These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.

Trends of incidence and prognosis of gastric neuroendocrine neoplasms: a study based on SEER and our multicenter research.

BACKGROUND: To investigate the recent epidemiological trends of gastric neuroendocrine neoplasms (GNENs) and establish a new tool to estimate the prognosis of gastric neuroendocrine carcinoma (GNEC) and gastric neuroendocrine tumor (GNET). METHODS: Nomograms were established based on a retrospective study on patients diagnosed with GNENs from 1975 to 2016 in Surveillance, Epidemiology and End Results database. External validation was performed among 246 GNENs patients in Jiangsu province to verify the discrimination and calibration of the nomograms. RESULTS: The age-adjusted incidence of GNENs has increased from 0.309 to 6.149 per 1,000,000 persons in the past 4 decades. Multivariate analysis indicated independent prognostic factors for both GNEC and GNET including age, distant metastasis and surgical intervention (P < 0.05). In addition, T, N staging and grade were significantly associated with survival of GNEC, while size was a predictor for GNET (P < 0.05). The C-indexes of the nomograms were 0.840 for GNEC and 0.718 for GNET, which were higher than those of the 8th AJCC staging system (0.773 and 0.599). Excellent discrimination was observed in the validation cohorts (C-index of nomogram vs AJCC staging for GNEC: 0.743 vs 0.714; GNET: 0.945 vs 0.927). Survival rates predicted by nomograms were close to the actual survival rates in the calibration plots in both training and validation sets. CONCLUSIONS: The incidence of the GNENs is increasing steadily in the past 40 years. We established more excellent nomograms to predict the prognosis of GNENs than traditional staging system, helping clinicians to make tailored decisions.

Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway.

Total 158 gonadotropin-type pituitary adenoma tissue specimens were collected and the expression of ESR1 in gonadotropin-type pituitary adenoma and its association with the overall survival of patients were analyzed. Transcriptome-sequencing data containing 79 cases of gonadotropin-type pituitary adenoma was used to search for all ESR1-related genes. KEGG pathway enrichment analysis was performed to identify the altering pathway and targeting genes. The in vitro and in vivo pituitary models were used to evaluate the therapeutic efficacy of estrogen receptor (ER) inhibitors AZD9496 and fulvestrant. The mechanism of AZD9496 and fulvestrant in suppressing pituitary adenoma were also investigated. Low-level ESR1 had longer progression-free survival (PFS) in pituitary adenoma patients. ErbB signaling pathway was discovered as the main enriched pathway. Furthermore, the STAT5B gene was identified as a key ESR-1-related gene. The expression of STAT5B was significantly positively correlated with ESR1 expression in the pituitary adenoma. AZD9496, a novel ER inhibitor, exhibited a potent inhibitory effect on the growth of in vitro and in vivo pituitary adenoma cells, and its efficacy is comparable to the classic ER inhibitor, fulvestrant. Mechanically, the AZD9496 and fulvestrant significantly blocked JAK2/STAT5B pathway in GT1-1 cells and xenograft mice. Our results provide substantial evidence for the subsequent clinical use of AZD9496 in the treatment of patients with pituitary adenoma.

Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes.

PURPOSE: Chordoma is a rare bone tumor with a high recurrence rate and limited treatment options. The aim of this study was to identify molecular subtypes of chordoma that may improve clinical management. EXPERIMENTAL DESIGN: We conducted RNA sequencing in 48 tumors from patients with Chinese skull-base chordoma and identified two major molecular subtypes. We then replicated the classification using a NanoString panel in 48 patients with chordoma from North America. RESULTS: Tumors in one subtype were more likely to have somatic mutations and reduced expression in chromatin remodeling genes, such as PBRM1 and SETD2, whereas the other subtype was characterized by the upregulation of genes in epithelial-mesenchymal transition and Sonic Hedgehog pathways. IHC staining of top differentially expressed genes between the two subtypes in 312 patients with Chinese chordoma with long-term follow-up data showed that the expression of some markers such as PTCH1 was significantly associated with survival outcomes. CONCLUSIONS: Our findings may improve the understanding of subtype-specific tumorigenesis of chordoma and inform clinical prognostication and targeted options.

PALB2 as a factor to predict the prognosis of patients with skull base chordoma.

Objective: This study aimed to study the role of PALB2 on the prognosis of skull base chordoma patients and the proliferation, migration, and invasion of chordoma cells. Methods: 187 patients with primary skull base chordoma were involved in the study. Immunohistochemical analysis was used to measure the PALB2 protein expression. Kaplan-Meier analysis, univariate and multivariate Cox analysis were used to evaluate the impact of PALB2 on patient prognosis. A nomogram was established for predicting the progression free survival of chordoma patients. Cell counting kit-8, colony formation, transwell migration, and invasion assays were used to assess the proliferation, migration, and invasion of chordoma cells with PALB2 knockdown. TIMER 2.0 was used to explore the expression and prognostic role of PALB2 in cancers. Results: High PALB2 expression indicated an adverse prognosis in chordoma. A nomogram involved PALB2, degree of resection, pathology, and Al-mefty classification could accurately predict the progression free survival of chordoma patients. The proliferation, migration, and invasion of chordoma cells significantly decreased after PALB2 knockdown. Additionally, PALB2 showed high expression in various cancers and was associated with a poor prognosis. Conclusion: In summary, our results reveal that high PALB2 expression indicates a poor prognosis of chordoma patients and promotes the malignant phenotypes of chordoma cells in vitro.

High systemic inflammation score is associated with adverse survival in skull base chordoma.

Background: The systemic inflammation score (SIS), based on preoperative lymphocyte to monocyte ratio (LMR) and albumin (ALB), was recently developed and is demonstrated to be a novel prognostic indicator in several cancers. However, data discussing the utility of SIS in chordoma are lacking. We aimed to investigate the distribution and the prognostic role of SIS in primary skull base chordoma patients undergoing surgery. Material and methods: Preoperative SIS was retrospectively collected from 183 skull base chordoma patients between 2008 and 2014 in a single center. Its associations with clinical features and overall survival (OS) were further analyzed. The SIS-based nomogram was developed and evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: The numbers of patients in the SIS 2, 1, and 0 group were 29 (15.8%), 60 (32.8%), 94 (51.4%), respectively. High SIS was associated with older age (p = 0.008), brainstem involvement of tumors (p = 0.039), and adverse OS (p < 0.001). Importantly, multivariate Cox analysis showed that high SIS independently predicts adverse OS. Furthermore, the nomogram based on SIS and clinical variables showed eligible performance for OS prediction in both training and validation cohorts. Conclusions: The SIS is a promising, simple prognostic biomarker, and the SIS-based nomogram serves as a potential risk stratification tool for outcome in skull base chordoma patients.

High Level of METTL7B Indicates Poor Prognosis of Patients and Is Related to Immunity in Glioma.

Glioma is the most common primary intracranial malignant tumor in adults. Although there have been many efforts on potential targeted therapy of glioma, the patient's prognosis remains dismal. Methyltransferase Like 7B (METTL7B) has been found to affect the development of a variety of tumors. In this study, we collected RNA-seq data of glioma in CGGA and TCGA, analyzed them separately. Then, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, and receiver operating characteristic curve (ROC curve) analysis were used to evaluate the effect of METTL7B on prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) enrichment analyses were used to identify the function or pathway associated with METTL7B. Moreover, the ESTIMATE algorithm, Cibersort algorithm, Spearman correlation analysis, and TIMER database were used to explore the relationship between METTL7B and immunity. Finally, the role of METTL7B was explored in glioma cells. We found that METTL7B is highly expressed in glioma, and high expression of METTL7B in glioma is associated with poor prognosis. In addition, there were significant differences in immune scores and immune cell infiltration between the two groups with different expression levels of METTL7B. Moreover, METTL7B was also correlated with immune checkpoints. Knockdown of METTL7B revealed that METTL7B promoted the progression of glioma cells. The above results indicate that METTL7B affects the prognosis of patients and is related to tumor immunity, speculating that METTL7B may be a new immune-related target for the treatment of glioma.

Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma.

BACKGROUND: The prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma. METHOD: Using a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients' survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines. RESULTS: Among 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p < 0.001). Knockdown of ASNS by small interfering RNA (siRNA) inhibited the growth, colony formation, migration and invasion of chordoma cells in vitro. CONCLUSION: This study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.

Loss of SMARCB1 promotes autophagy and facilitates tumour progression in chordoma by transcriptionally activating ATG5.

OBJECTIVES: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) loss is associated with a poor prognosis in chordoma, while the mechanism remains largely unclear. Here, we aim to explore the function and regulatory mechanisms of SMARCB1 in chordoma. MATERIALS AND METHODS: The effect of SMARCB1 on chordoma cells was investigated in vitro and in vivo. Chromatin immunoprecipitation (ChIP) sequencing was used to investigate the mechanisms of SMARCB1 in chordoma. The association between SMARCB1 and autophagy was validated by Western blot, immunofluorescence and transmission electron microscopy. In addition, the ATG5 expression in chordoma tissue was assessed using immunohistochemistry and correlated with patient survival. RESULTS: SMARCB1 inhibited the malignant phenotype of chordoma cells in vitro and in vivo, supporting a tumour suppressor role of SMARCB1 in chordoma. ATG5-mediated autophagy was identified as a potential downstream pathway of SMARCB1. Mechanistically, SMARCB1 bound directly to the ATG5 promoter and epigenetically inhibited its transcription, which decreased ATG5 expression and impaired autophagy. Additionally, autophagy inhibitor chloroquine had a potential anti-cancer effect on chordoma cells in vitro. Moreover, high ATG5 expression was observed in recurrent chordoma patients, which independently correlated with adverse outcomes. CONCLUSIONS: Taken together, our results revealed that the SMARCB1/ATG5 axis is a promising therapeutic target for chordoma and autophagy inhibitors may be effective agents for chordoma treatment.

High Red Cell Distribution Width Independently Predicts Adverse Survival in Patients with Newly Diagnosed Skull Base Chordoma.

OBJECTIVE: Accumulating studies report that levels of mean corpuscular volume (MCV) and red cell distribution width (RDW) are associated with outcomes in cancer patients, while studies including MCV and RDW in chordoma are lacking so far. Therefore, our study aims to investigate the prognostic impact of MCV and RDW on survival in skull base chordoma patients. METHODS: Levels of preoperative MCV and RDW in 187 primary skull base chordoma patients were collected. X-tile software was used to find the cutoff values of MCV and RDW. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan-Meier methods, Cox analysis, and nomogram model. RESULTS: Low MCV level (MCV <84.2) was more commonly observed in classical chordoma patients (p=0.022). High RDW level (RDW≥12.7) was correlated with older patient age (p=0.022) and a tough tumor texture (p=0.035). Low MCV level and high RDW level were associated with poor PFS (p=0.045 and 0.007, respectively) and OS (p=0.023 and <0.001, respectively). Multivariate Cox analysis demonstrated that RDW was an independent prognostic indicator for both PFS (p=0.001) and OS (p<0.001). Importantly, a nomogram based on RDW and clinical predictors showed satisfactory performance for PFS and OS prediction (concordance index, C-index: 0.684 and 0.744, respectively). CONCLUSION: Our data was first to reveal the prognostic role of RDW in skull base chordoma, and identified the use of RDW may contribute to a more accurate prognosis judgment and personalized treatment decision.

Endoscopic Endonasal Surgical Strategy for Skull Base Chordomas Based on Tumor Growth Directions: Surgical Outcomes of 167 Patients During 3 Years.

BACKGROUND: Skull base chordomas (SBCs) are rare malignant bone tumors with dismal long-term local control. Endoscopic endonasal surgeries (EESs) are increasingly adopted to resect SBCs recently. Gross total resection (GTR) favors good outcomes. However, the SBCs often invade the skull base extensively and hide behind vital neurovascular structures; the tumors were challenging to remove entirely. To improve the GTR, we established a surgical strategy for EES according to the tumor growth directions. METHODS: A total of 112 patients with SBCs from 2018 to 2019 were classified into the derivation group. We retrospectively analyzed their radiologic images and operation videos to find the accurate tumor locations. By doing so, we confirmed the tumor growth directions and established a surgical strategy. Fifty-five patients who were operated on in 2020 were regarded as the validation group, and we performed their operations following the surgical strategy to verify its value. RESULTS: In the derivation group, 78.6% of SBCs invade the dorsum sellae and posterior clinoid process region. 62.5% and 69.6% of tumors extend to the left and right posterior spaces of cavernous ICA, respectively. 59.8% and 61.6% of tumors extend to the left and right posterior spaces of paraclival and lacerum ICA (pc-la ICA), respectively. 30.4% and 28.6% of tumors extended along the left and right petroclival fissures that extend toward the jugular foramen, respectively. 30.4% of tumors involved the foramen magnum and craniocervical junction region. The GTR was achieved in 60.8% of patients with primary SBCs in the derivation group. Based on the tumors' growth pattern, pituitary transposition and posterior clinoidectomy techniques were adopted to resect tumors that hid behind cavernous ICA. Paraclival ICA transposition was used when the tumor invaded the posterior spaces of pc-la ICA. Lacerum fibrocartilage resection and eustachian tube transposition may be warranted to resect the tumors that extended to the jugular foramen. GTR was achieved in 75.0% of patients with primary SBCs in the validation group. CONCLUSION: Besides the midline clival region, the SBCs frequently grow into the eight spaces mentioned above. The surgical strategy based on the growth pattern contributes to increasing the GTR rate.

MiR-152-5p as a microRNA passenger strand special functions in human gastric cancer cells.

Gastric cancer (GC) is one of the most common malignancies with high mortality rate. MiR-152 may exert the function of tumor suppressor by regulating its target gene, including PIK3CA. Nevertheless, all of the described functions are referred explicitly to miR-152-3p, while miR-152-5p as a passenger strand is poorly realized and entirely ignored. We previously selected miR-152-5p as a candidate using cell migration inhibition screening for GC cells and predicted that miR-152-5p might also target PIK3CA. In this study, we found an abnormal proportion of miR-152-3p / miR-152-5p in GC (gastric cancer) tissues and cells and demonstrated that miR-152-5p had poorer stability in GC cells, revealing the possibility that miR-152-5p is abnormally "suppressed" in gastric cancer. We also investigated and confirmed the role of miR-152-5p in GC by a series of experiments, and found that miR-152-5p modulated cell viability, migration, invasion, and cell-cycle progression of human GC cells, and also inhibited tumor growth and metastasis in vivo partially by targeting PIK3CA. More interestingly, it was proved that miR-152-3p and miR-152-5p had synergistic effects on the inhibition of PIK3CA in GC cells. The results of this study suggest that miR-152-5p may act as a tumor suppressor in SGC-7901 gastric cancer cells via targeting PIK3CA. Further, the study provides a novel insight into the roles of miRNA* during carcinogenesis.