The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

A Rare Case of Sinonasal Pleomorphic Adenoma.

Pleomorphic adenoma (PA) is the most prevalent benign tumor of the salivary glands, characterized by both epithelial and mesenchymal differentiation. It primarily originates within the parotid and submandibular glands, with only rare occurrences in the minor salivary glands. PA in the sinonasal area is extremely rare. Herein, we present a case of a 61-year-old female with a large soft tissue mass in the paranasal sinus and nasal cavity, as evidenced by computed tomography imaging. The patient suffered from repeated nasal congestion for more than 6 months. Eventually, the mass was completely resected using an endoscopic endonasal prelacrimal approach under general anesthesia. Postoperative pathological examination revealed the presence of PA in the nasal sinus.

Cross-talk between PARN and EGFR-STAT3 Signaling Facilitates Self-Renewal and Proliferation of Glioblastoma Stem Cells.

Glioblastoma is the most common type of malignant primary brain tumor and displays highly aggressive and heterogeneous phenotypes. The transcription factor STAT3 has been reported to play a key role in glioblastoma malignancy. Thus, discovering targets and functional downstream networks regulated by STAT3 that govern glioblastoma pathogenesis may lead to improved treatment strategies. In this study, we identified that poly(A)-specific ribonuclease (PARN), a key modulator of RNA metabolism, activates EGFR-STAT3 signaling to support glioblastoma stem cells (GSC). Functional integrative analysis of STAT3 found PARN as the top-scoring transcriptional target involved in RNA processing in patients with glioblastoma, and PARN expression was strongly correlated with poor patient survival and elevated malignancy. PARN positively regulated self-renewal and proliferation of GSCs through its 3'-5' exoribonuclease activity. EGFR was identified as a clinically relevant target of PARN in GSCs. PARN positively modulated EGFR by negatively regulating the EGFR-targeting miRNA miR-7, and increased EGFR expression created a positive feedback loop to increase STAT3 activation. PARN depletion in GSCs reduced infiltration and prolonged survival in orthotopic brain tumor xenografts; similar results were observed using siRNA nanocapsule-mediated PARN targeting. Pharmacological targeting of STAT3 also confirmed PARN regulation by STAT3 signaling. In sum, these results suggest that a STAT3-PARN regulatory network plays a pivotal role in tumor progression and thus may represent a target for glioblastoma therapeutics. SIGNIFICANCE: A positive feedback loop comprising PARN and EGFR-STAT3 signaling supports self-renewal and proliferation of glioblastoma stem cells to drive tumor progression and can be targeted in glioblastoma therapeutics.

[Removal of Cr(â ¥) via a Nickel Ferrite@Activated Carbon Composite Under Batch Experiments: Study of Characterization, Performance, and Mechanism].

A magnetic activated carbon adsorbent named NiFe2O4@AC was synthesized by modifying activated carbon with NiFe2O4 and used for the adsorption of Cr(Ⅵ) ions from waste water. The influencing factors, adsorption kinetics, and adsorption isotherms of Cr(Ⅵ) adsorption by the adsorbent were investigated. The results showed that the removal rate of Cr(Ⅵ) adsorption by NiFe2O4@AC reached 96.92%, and the adsorption amount reached 72.62 mg·g-1 at the adsorption conditions of temperature (298 K), pH 2, Cr(Ⅵ) initial concentration (150 mg·L-1), adsorbent dosage (0.1 g), and contact time (720 min). The experimental data were best described by the proposed secondary kinetics and Langmuir model, indicating that the adsorption process was a monolayer chemisorption process. The increase in temperature favored the adsorption of Cr(Ⅵ) on NiFe2O4@AC because the adsorption process was a spontaneous, heat-absorbing reaction. The adsorption mechanism of NiFe2O4@AC was mainly through complexation and electrostatic attraction to adsorb Cr(Ⅵ); meanwhile, the applied magnetic field could be separated from the solution, which has good application prospects.

Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study.

OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron. RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake. CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2.

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

A novel monoclonal antibody associated with glucoside kills gastric adenocarcinoma AGS cells based on glycosylation target.

Glycosylation results in the production of glycans which are required for certain proteins to function. These glycans are also present on cell surfaces where they help maintain cell membrane integrity and are a key component of immune recognition. As such, cancer has been shown to alter glycosylation to promote tumour proliferation, invasion, angiogenesis, and immune envasion. Currently, there are few therapeutic monoclonal antibodies (mAb) which target glycosylation alterations in cancer. Here, we report a novel mAb associated with a glucoside, mAb 201E4, which is able induce cancer cell death and apoptosis based on a specific glycosylation target. This mAb evokes cancer cell death in vitro via caspase, fas, and mitochondrial associated apoptotic pathways. The efficacy of this mAb was further confirmed in vivo as treatment of mice with mAb 201E4 resulted in potent tumour shrinkage. Finally, the antibody was proven to be specific to glycosylation alterations in cancer and have no binding to normal tissues. This data indicates that mAb 201E4 successfully targets glycosylation alterations in neoplasms to induce cancer cell death, which may provide a new strategy for therapy in cancer.

The prognostic significance of ß-Catenin expression in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis.

Background: ß-Catenin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here, we conduct a meta-analysis to better clarify the correlation between ß-Catenin expression and survival outcomes in nasopharyngeal carcinoma (NPC) patients. Patients/methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for relevant studies to explore the prognostic significance of ß-Catenin in NPC. Pooled hazards ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association of ß-Catenin expression with survival outcomes in NPC patients. Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were also statistically analyzed. Results: Eight studies involving 1,179 patients with NPC were ultimately included in the meta-analysis. Pooled analysis indicated that elevated ß-Catenin expression was significantly associated with poor OS (HR = 2.45, 95% CIs: 1.45-4.16, p = 0.001) and poor DFS/PFS (HR 1.79, 95% CIs: 1.29-2.49, p = 0.000). Furthermore, ß-cadherin was signifcantly associated with higher TMN stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000), clinical stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000) and lymph node metastasis (LNM) (OR = 5.01, 95% CIs 2.40-10.44, p = 0.000). Conclusions: This study demonstrated that for NPC, patients with elevated ß-Catenin expression are more likely to have poor survival.

The MAP3K1/c-JUN signaling axis regulates glioblastoma stem cell invasion and tumor progression.

Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.

Oncocytoma-Related Gene Signature to Differentiate Chromophobe Renal Cancer and Oncocytoma Using Machine Learning.

Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.

The prognostic value of m6A-related LncRNAs in patients with HNSCC: bioinformatics analysis of TCGA database.

N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan-Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.

Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways.

Background: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear. Methods: The mRNA expression data and clinical information of GBM and normal tissues were collected from the Chinese Glioma Genome Atlas The Cancer Genome Atlas (TCGA), and REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) cohorts. The DESeq2 R package was used to identify the differentially expressed genes between primary and recurrent GBM. ClueGO, Kyoto Encyclopedia of Genes and Genomes (KEGG), Biological Process in Gene ontology (GO-BP), and the Protein ANalysis THrough Evolutionary Relationships (PANTHER) pathway analyses were performed to explore the enriched signaling pathways in upregulated DEGs in recurrent GBM. A gene list that contained potential oncogenes that showed a significant negative correlation with patient survival from The Cancer Genome Atlas was used to further screen driver candidates for recurrent GBM. Univariate Cox proportional hazards regression analyses were used to investigate the risk score for the mRNA expression of the candidates. Single-cell RNA sequencing (scRNA-Seq) analyses were used to determine the cell type-specific distribution of Fc gamma receptor II b (FcγRIIb) in GBM. Immunohistochemistry (IHC) was used to confirm the FcγRIIb-positive cell populations in primary and paired recurrent GBM. Results: Through DEG analysis and overlap analysis, a total of 10 genes that are upregulated in recurrent GBM were screened. Using validation databases, FcγRIIb was identified from the 10 candidates that may serve as a driver for recurrent GBM. FCGR2B expression, not mutation, further showed a highly negative correlation with the poor prognosis of patients with recurrent GBM. Furthermore, scRNA-Seq analyses revealed that tumor-associated macrophage- and dendritic cell-specific FCGR2B was expressed. Moreover, FcγRIIb also showed a strong positive correlation coefficient with major immune-associated signaling pathways. In clinical specimens, FcγRIIb-positive cell populations were higher in recurrent GBM than in primary GBM. Conclusion: This study provides novel insights into the role of FcγRIIb in recurrent GBM and a promising strategy for treatment as an immune therapeutic target.

Applying Artificial Intelligence to Gynecologic Oncology: A Review.

IMPORTANCE: Artificial intelligence (AI) will play an increasing role in health care. In gynecologic oncology, it can advance tailored screening, precision surgery, and personalized targeted therapies. OBJECTIVE: The aim of this study was to review the role of AI in gynecologic oncology. EVIDENCE ACQUISITION: Artificial intelligence publications in gynecologic oncology were identified by searching "gynecologic oncology AND artificial intelligence" in the PubMed database. A review of the literature was performed on the history of AI, its fundamentals, and current applications as related to diagnosis and treatment of cervical, uterine, and ovarian cancers. RESULTS: A PubMed literature search since the year 2000 showed a significant increase in oncology publications related to AI and oncology. Early studies focused on using AI to interrogate electronic health records in order to improve clinical outcome and facilitate clinical research. In cervical cancer, AI algorithms can enhance image analysis of cytology and visual inspection with acetic acid or colposcopy. In uterine cancers, AI can improve the diagnostic accuracies of radiologic imaging and predictive/prognostic capabilities of clinicopathologic characteristics. Artificial intelligence has also been used to better detect early-stage ovarian cancer and predict surgical outcomes and treatment response. CONCLUSIONS AND RELEVANCE: Artificial intelligence has been shown to enhance diagnosis, refine clinical decision making, and advance personalized therapies in gynecologic cancers. The rapid adoption of AI in gynecologic oncology will depend on overcoming the challenges related to data transparency, quality, and interpretation. Artificial intelligence is rapidly transforming health care. However, many physicians are unaware that this technology is being used in their practices and could benefit from a better understanding of the statistics and computer science behind these algorithms. This review provides a summary of AI, its applicability, and its limitations in gynecologic oncology.

Acylation of non-specific phospholipase C4 determines its function in plant response to phosphate deficiency.

Non-specific phospholipase C (NPC) is involved in plant growth, development and stress responses. To elucidate the mechanism by which NPCs mediate cellular functions, here we show that NPC4 is S-acylated at the C terminus and that acylation determines its plasma membrane (PM) association and function. The acylation of NPC4 was detected using NPC4 isolated from Arabidopsis and reconstituted in vitro. The C-terminal Cys-533 was identified as the S-acylation residue, and the mutation of Cys-533 to Ala-533 in NPC4 (NPC4C533A ) led to the loss of S-acylation and membrane association of NPC4. The knockout of NPC4 impeded the phosphate deficiency-induced decrease of the phosphosphingolipid glycosyl inositol phosphoryl ceramide (GIPC), but introducing NPC4C533A to npc4-1 failed to complement this defect, thereby supporting the hypothesis that the non-acylated NPC4C533A fails to hydrolyze GIPC during phosphate deprivation. Moreover, NPC4C533A failed to complement the primary root growth in npc4-1 under stress. In addition, NPC4 in Brassica napus was S-acylated and mutation of the S-acylating cysteine residue of BnaC01.NPC4 led to the loss of S-acylation and its membrane association. Together, our results reveal that S-acylation of NPC4 in the C terminus is conserved and required for its membrane association, phosphosphingolipid hydrolysis and function in plant stress responses.

Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10-15), sNTFRII (4.8, p<10-8) and MMP2 (4.5, p<10-5). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies.

Tumor-intrinsic and -extrinsic (immune) gene signatures robustly predict overall survival and treatment response in high grade serous ovarian cancer patients.

In the present study, we developed a transcriptomic signature capable of predicting prognosis and response to primary therapy in high grade serous ovarian cancer (HGSOC). Proportional hazard analysis was performed on individual genes in the TCGA RNAseq data set containing 229 HGSOC patients. Ridge regression analysis was performed to select genes and develop multigenic models. Survival analysis identified 120 genes whose expression levels were associated with overall survival (OS) (HR = 1.49-2.46 or HR = 0.48-0.63). Ridge regression modeling selected 38 of the 120 genes for development of the final Ridge regression models. The consensus model based on plurality voting by 68 individual Ridge regression models classified 102 (45%) as low, 23 (10%) as moderate and 104 patients (45%) as high risk. The median OS was 31 months (HR = 7.63, 95% CI = 4.85-12.0, P < 1.0-10) and 77 months (HR = ref) in the high and low risk groups, respectively. The gene signature had two components: intrinsic (proliferation, metastasis, autophagy) and extrinsic (immune evasion). Moderate/high risk patients had more partial and non-responses to primary therapy than low risk patients (odds ratio = 4.54, P < 0.001). We concluded that the overall survival and response to primary therapy in ovarian cancer is best assessed using a combination of gene signatures. A combination of genes which combines both tumor intrinsic and extrinsic functions has the best prediction. Validation studies are warranted in the future.

Retrospective Validation of a 168-Gene Expression Signature for Glioma Classification on a Single Molecule Counting Platform.

Gene expression profiling has been shown to be comparable to other molecular methods for glioma classification. We sought to validate a gene-expression based glioma classification method. Formalin-fixed paraffin embedded tissue and flash frozen tissue collected at the Augusta University (AU) Pathology Department between 2000-2019 were identified and 2 mm cores were taken. The RNA was extracted from these cores after deparaffinization and bead homogenization. One hundred sixty-eight genes were evaluated in the RNA samples on the nCounter instrument. Forty-eight gliomas were classified using a supervised learning algorithm trained by using data from The Cancer Genome Atlas. An ensemble of 1000 linear support vector models classified 30 glioma samples into TP1 with classification confidence of 0.99. Glioma patients in TP1 group have a poorer survival (HR (95% CI) = 4.5 (1.3-15.4), p = 0.005) with median survival time of 12.1 months, compared to non-TP1 groups. Network analysis revealed that cell cycle genes play an important role in distinguishing TP1 from non-TP1 cases and that these genes may play an important role in glioma survival. This could be a good clinical pipeline for molecular classification of gliomas.

Are There Survival Differences Between Women with Equivalent Residual Disease After Interval Cytoreductive Surgery Compared with Primary Cytoreductive Surgery for Advanced Ovarian and Peritoneal Cancer?

OBJECTIVE: The aim of this study was to investigate survival differences between equivalent residual disease [complete gross resection (CGR), minimal residual disease (MRD), suboptimal] at the time of primary debulking surgery (PDS) and interval debulking surgery (IDS). METHODS: The National Cancer Database was used to identify patients from 2010 to 2015 with stage IIIC/IV primary peritoneal or ovarian cancer who had residual disease recorded. Propensity score matching (PSM) was used to correct for differences in characteristics between the PDS and IDS groups. RESULTS: Of 8683 patients with advanced ovarian cancer, 4493 (52%), 2546 (29%), and 1644 (19%) had CGR, MRD, or suboptimal resection, respectively. From 2010 to 2015, the number of patients undergoing IDS increased 27% (ptrend < 0.001), and there was an 18% increase in CGRs (ptrend = 0.005). The increased use of IDS from 2010 to 2015 was associated with increased CGRs (ptrend = 0.02) and decreased MRD (ptrend = 0.001), but not with decreased suboptimal resections (ptrend = 0.18). IDS, even after PSM, was associated with inferior overall survival [OS; hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.03-1.22, p = 0.008]. A CGR at PDS had prolonged median OS compared with a CGR at IDS (51 vs. 44 months, p < 0.001). Additionally, MRD at PDS had worse median OS compared with a CGR at IDS (41 vs. 44 months, p = 0.03), but improved median OS compared with MRD at IDS (median OS 35 months, p = 0.05). CONCLUSION: The use of IDS continues to rise in the US, and is associated with improved surgical outcomes but not necessarily similar oncologic outcomes. There should be continued efforts to improve cytoreductive outcomes in women with advanced ovarian and peritoneal malignancies.

Comparative analysis of transcriptomic profile, histology, and IDH mutation for classification of gliomas.

Gliomas are currently classified through integration of histology and mutation information, with new developments in DNA methylation classification. However, discrepancies exist amongst the major classification methods. This study sought to compare transcriptome-based classification to the established methods. RNAseq and microarray data were obtained for 1032 gliomas from the TCGA and 395 gliomas from REMBRANDT. Data were analyzed using unsupervised and supervised learning and other statistical methods. Global transcriptomic profiles defined four transcriptomic glioma subgroups with 91.4% concordance with the WHO-defined mutation subtypes. Using these subgroups, 168 genes were selected for the development of 1000 linear support vector classifiers (LSVC). Based on plurality voting of 1000 LSVC, the final ensemble classifier confidently classified all but 17 TCGA gliomas to one of the four transcriptomic profile (TP) groups. The classifier was validated using a gene expression microarray dataset. TP1 cases include IDHwt, glioblastoma high immune infiltration and cellular proliferation and poor survival prognosis. TP2a is characterized as IDHmut-codel, oligodendrogliomas with high tumor purity. TP2b tissue is mostly composed of neurons and few infiltrating malignant cells. TP3 exhibit increased NOTCH signaling, are astrocytoma and IDHmut-non-codel. TP groups are highly concordant with both WHO integrated histology and mutation classification as well as methylation-based classification of gliomas. Transcriptomic profiling provides a robust and objective method to classify gliomas with high agreement to the current WHO guidelines and may provide additional survival prediction to the current methods.