Oncogenesis Of Tumors Research Articles

Cellular Regulation and Oncogenesis of Primary Tumors in the Central Nervous System

AbstractThe World Health Organization's system for classifying and grading primary tumors of the Central Nervous System conjectures the clinical-biological course of the oncogenic process based on morphological, genetic, histological, and immunohistochemical parameters. These principles are fundamental for a progression in the classification of these tumors, to guarantee the promotion of a more precise diagnosis. In this sense, it is important to understand the process of oncotic cell formation, which is the result of mutations in intra and extracellular control pathways. In this way, genes that act to induce the cell cycle, under normal conditions, when mutated, can result in a dysregulation of the progress of the cycle, causing alterations in the control factors and, consequently, phenotypic transformations in the cell. Thus, to understand the role of genes in modulating primary tumors in the Central Nervous System, mutations in the genes most prevalently related to Gliomas, Meningiomas, and Medulloblastomas were addressed highlighting their influences on the development of these tumors.

Immune Modulation by Epstein-Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis.

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV's lytic phase contribution to oncogenesis.

Cuproptosis-related gene-located DNA methylation in lower-grade glioma: Prognosis and tumor microenvironment.

Cuproptosis a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among DNA-methylation located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients.

In Silico Search for Drug Candidates Targeting the PAX8-PPARγ Fusion Protein in Thyroid Cancer.

The PAX8/PPARγ rearrangement, producing the PAX8-PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble-docking-based compound screening. Specifically, we investigated the pocket structure that should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand-binding pocket on the PPARγ side of the PPFP is similar to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to the PPFP for 97 drug or drug-like compounds registered in the DrugBank database with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics Poisson-Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

Multi-omics pan-cancer analyses identify MCM4 as a promising prognostic and diagnostic biomarker

Minichromosome Maintenance Complex Component 4 (MCM4) is a vital component of the mini-chromosome maintenance complex family, crucial for initiating the replication of eukaryotic genomes. Recently, there has been a growing interest in investigating the significance of MCM4 in different types of cancer. Despite the existing research on this topic, a comprehensive analysis of MCM4 across various cancer types has been lacking. This study aims to bridge this knowledge gap by presenting a thorough pan-cancer analysis of MCM4, shedding light on its functional implications and potential clinical applications. The study utilized multi-omics samples from various databases. Bioinformatic tools were employed to explore the expression profiles, genetic alterations, phosphorylation states, immune cell infiltration patterns, immune subtypes, functional enrichment, disease prognosis, as well as the diagnostic potential of MCM4 and its responsiveness to drugs in a range of cancers. Our research demonstrates that MCM4 is closely associated with the oncogenesis, prognosis and diagnosis of various tumors and proposes that MCM4 may function as a potential biomarker in pan-cancer, providing a deeper understanding of its potential role in cancer development and treatment.

Low expression of RACK1 is associated with metastasis and worse prognosis in cholangiocarcinoma

BackgroundCholangiocarcinoma is a poorly prognostic malignant tumor, and the metastatic stage of cancer is not an early stage when diagnosed. Lymph node metastasis is common in the early stage. Ribosomal receptor for activated C-kinase 1 (RACK1) has found involved in the oncogenesis of various tumors and in the epithelial-mesenchymal transition (EMT). Nevertheless, its role in cholangiocarcinoma remains unknown. Material and methodsThe possible correlation between RACK1 and tumor prognosis was analyzed in cholangiocarcinoma patients. The GEO and TCGA databases were used to evaluate the level of RACK1 in cholangiocarcinoma. The RBE and HCCC-9810 cell lines were used to examine the effects of RACK1 in the behavior of tumor cells in vitro. ResultsThe Kaplan-Meier analysis indicated that low expression of RACK1 was associated with poor prognosis and RACK1 was negatively related to lymph node metastasis, which were verified in databases TCGA and GEO; downregulation of RACK1 via RNA interference correlated with changes in the expression of EMT biomarkers and promoted the migration of cholangiocarcinoma cell lines. ConclusionThe protein expression of RACK1 is significantly higher in cholangiocarcinoma tissues than in peritumoral tissues, however, the high RACK1 expression indicates better overall survival and less risk for lymph node metastasis. In vitro, RACK1 may suppress the migratory ability of cholangiocarcinoma cells by inhibiting EMT.

Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity.

Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.

Predicting prognosis and immune status in sarcomas by identifying necroptosis-related lncRNAs.

Sarcomas are a type of highly heterogeneous malignant tumors originating from mesenchymal tissues. Necroptosis is intricately connected to the oncogenesis and progression of tumors. The main goal of this research is to assess the prognostic value of necroptosis-related lncRNAs (NRlncRNAs) in sarcomas and to develop a risk model based on NRlncRNAs to evaluate prognostic and immune status of the sarcomas. We screened NRlncRNAs using the gene co-expression network, developed a prognostic risk model of sarcomas, and then verified the model. Following that, various bioinformatics analysis algorithms were employed to analyze the distinct characteristics of patients of the risk model. Furthermore, the function and regulatory mechanism of NRlncRNA SNHG6 in sarcomas were investigated through osteosarcoma cell experiments, such as qRT-PCR, Western blot, CCK-8, clone formation, and transwell assay. We successfully developed a NRlncRNAs-related prognostic risk model and screened 5 prognosis-related NRlncRNAs, with SNGH6 being the most significant for prognosis of patients. According to results, the significant differences exist in prognosis, clinical characteristics, and tumor immune status among patients of the risk model. The experiments of osteosarcoma cells demonstrated that NRlncRNA SNHG6 knockdown significantly attenuated the cells' proliferation, migration, and invasion. qRT-PCR and WB results showed that SNHG6 regulated AXL and AKT signaling. We have developed an innovative investigation on NRlncRNAs, which can serve as a reference for diagnosis, therapy, and prognosis of sarcomas. Additionally, we demonstrated that NRlncRNA SNHG6 regulated AXL and AKT signaling in osteosarcoma cells and the proliferation, migration, and invasion of tumor cells.

ARID5B promoted the histone demethylation of SORBS2 and hampered the metastasis of ovarian cancer

Ovarian cancer (OVCA) is the 4th most common female tumor after breast cancer, cervical cancer, and endometrial cancer, and now is mainly treated with debulking surgery and postoperative cisplatin and paclitaxel-based combination chemotherapy regimens. However, OVCA is insidious in its development and recurrence occurred in some patients after treatment. It is of great significance to study the pathogenesis of ovarian cancer and identify more biomarkers. Recently, the role of histone methyltransferase (HMT) and histone demethylase (HDM) in oncogenesis and development of malignant tumors has raised attention. Unlike other JMJC demethylases that have both JMJC and ARID domains in a single molecule, PHF2 requires assembly into a complex with a DNA-binding subunit (ARID5B) and exerts its enzymatic activity. Therefore, the aim of this manuscript is to investigate the role of histone demethylases ARID5B-PHF2 complex in the metastasis of OVCA. As result, we found ARID5B and PHF2 are both low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. Also, ARID5B suppressed rearrangement of the cytoskeleton in the process of EMT in OVCA cell lines. The role of PHF2 as a tumor suppressor was also confirmed both in vivo and in vitro. SORBS2 is low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. The expression of SORBS2 is positively corelated with the expression of ARID5B and PHF2. The promoter of SORBS2 is proved combined with ARID5B. The expression of SORBS2 was increased due to ARID5B-PHF2 complex promoted the histone demethylation by mainly binding in site H3K36me2 and therefore promoting the transcription of SORBS2. In conclusion, ARID5B-PHF2 complex promoted the histone demethylation of SORBS2 by mainly bind in site H3K36me2 and therefore promote the transcription of SORBS2 then hampered the process of EMT and tumor generation of OVCA. These results provided a new perspective on the molecular mechanisms of OVCA development and offered a new target of clinical diagnose and treatment of OVCA.

Ribosomal protein L8 regulates the expression and splicing pattern of genes associated with cancer-related pathways.

Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. RPL8-OE inhibited cell proliferation and promoted cell apoptosis. RPL8 regulated the differential expression of many oncogenic genes and the occurrence of RASEs. Many DEGs and RASE genes (RASGs) were enriched in tumorigenesis and tumor progression-related pathways, including angiogenesis, inflammation, and regulation of cell proliferation. RPL8 could regulate the RASGs enriched in the negative regulation of apoptosis, consistent with its proapoptosis function. Furthermore, RPL8 may influence cancer-related DEGs by modulating the alternative splicing of transcription factors. RPL8 might affect the phenotypes of cancer cells by altering the transcriptome profiles, including gene expression and splicing, which provides novel insights into the biological functions of RPL8 in tumor development.

Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors.

Inositol polyphosphate-4-phosphatase type II (INPP4B) is a newly discovered PI(3,4,5)P3 phosphatase. Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system, and the abnormal expression of INPP4B may be attributed to the occurrence, development, and prognosis of tumors of the digestive system. This paper reviews studies on the correlations between INPP4B and digestive system tumors and the roles of INPP4B in the development of different tumors to provide a theoretical basis for further research on its molecular mechanism and clinical application. "INPP4B" and "tumor" were searched as key words in PubMed and in the CNKI series full text database retrieval system from January 2000 to August 2023. A total of 153 English-language studies and 30 Chinese-language studies were retrieved. The following enrollment criteria were applied: (1) Studies contained information on the biological structure and functions of INPP4B; (2) studies covered the influence of abnormal expression of INPP4B in digestive system tumors; and (3) studies covered the role of INPP4B in the diagnosis, treatment, and prognosis of digestive system tumors. After excluding the literature irrelevant to this study, 61 papers were finally included in the analysis. INPP4B expression is low in gastric cancer, colon cancer, pancreatic cancer, and liver cancer but it has high expression in esophageal cancer, colon cancer, pancreatic cancer, and gallbladder cancer. INPP4B is involved in the occurrence and development of digestive system tumors through the regulation of gene expression and signal transduction. The abnormal expression of INPP4B plays an important role in the development of digestive system tumors. Studies on INPP4B provide new molecular insights for the diagnosis, treatment, and prognosis evaluation of digestive system tumors.

PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program. Phosphoenolpyruvate carboxylase 1 (PCK1), a gluconeogenic metabolic enzyme, is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis. The oncogenesis and progression of tumors are closely related to cancer stem cells. It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma. Herein, the results showed that PCK1 inhibited the self-renewal property of hepatoma cells, reduced the mRNA level of cancer stem cell markers, and inhibited tumorigenesis. Moreover, PCK1 increased the sensitivity of hepatocellular carcinoma cells to sorafenib. Furthermore, we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation. Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib. Thus, combined treatment with verteporfin and sorafenib may be a potential anti-tumor strategy in hepatocellular carcinoma.

SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.

Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.

Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the oncogenesis and progression of tumors, pyroptosis is crucial, and complex withal. Currently, pyroptosis is the focus topic in the research field of oncology, but there is no single bibliometric analysis systematically studying 'pyroptosis and cancer'. Our study aimed to visualize the research status of pyroptosis in oncology and excavate the hotspots and prospects in this field. Furthermore, in consideration of the professional direction of researchers, we particularly emphasized articles on pyroptosis in gynecology and formed a mini systematic review. This bibliometric work integrated and analyzed all articles from ISI Web of Science: Science Citation Index Expanded (SCI-Expanded) (dated April 25th, 2022), based on quantitative and visual mapping approaches. Systematically reviewing articles on pyroptosis in gynecology helped us complement our analysis of research advancements in this field. Including 634 articles, our study found that the number of articles on pyroptosis in cancer increased exponentially in recent years. These publications came from 45 countries and regions headed by China and the US mainly aiming at the mechanism of pyroptosis in cell biology and biochemistry molecular biology, as well as the role of pyroptosis in the development and therapeutic application of various cancers. The top 20 most cited studies on this topic mostly came from the US, followed by China and England, and half of the articles cited more than 100 times in total were published in Nature. Moreover, as for gynecologic cancer, in vitro and bioinformatics analysis were the main methodology conducting to explore roles of pyroptosis-related genes (PRGs) and formation of inflammasomes in cancer progression and prognosis. Pyroptosis has evolved into a burgeoning research field in oncology. The cellular and molecular pathway mechanism of pyroptosis, as well as the effect of pyroptosis in oncogenesis, progression, and treatment have been the hot topic of the current study and provided us the future direction as the potential opportunities and challenges. We advocate more active cooperation to improve therapeutic strategies for cancer.

INNV-13. INDOLENT H3 K27-ALTERED DIFFUSE MIDLINE GLIOMA

Abstract INTRODUCTION H3 K27-altered diffuse midline glioma (DMG) is an aggressive central nervous system tumor that is universally fatal with a median survival of 8-12 months after diagnosis. Here we present a patient who was incidentally found to have a lesion within the right thalamus on brain magnetic resonance imaging (MRI). Twelve years later, she was found to have a brain mass within the same area with pathology consistent with an H3 K27-altered DMG. Case Description: A 14-year-old female presented with new onset left sided numbness and weakness, blurry vision and a right sided temporal headache. Her past medical history is significant for severe persistent asthma and anoxic brain injury secondary to a cardiopulmonary arrest at 2-years-of-age due to an asthma exacerbation. She has had multiple MRIs of her brain since her initial insult which initially showed the presence of a T2/FLAIR hyperintense lesion within the right medial thalamus in addition to chronic central nervous system changes. The right thalamic lesion was stable in size between images obtained at 2-years and 4-years of age. Her current physical exam is significant for decreased strength to her left upper and lower extremities. Brain MRI with and without contrast is obtained, demonstrating partial effacement of the third ventricle due to mass effect from an enlarging mass from the right thalamus. Biopsy of the lesion demonstrated an H3 K27-altered DMG, WHO grade 4. Our patient went on to receive palliative radiation therapy with 59.4 Gy over 33 fractions. DISCUSSION This case illustrates an unusual presentation of an H3 K27-altered DMG with an indolent course, diagnosed twelve years after the initial MRI finding. This proposes the possibility of multiple factors playing a role in the oncogenesis of these aggressive tumors and that further research is warranted.

Development and validation of novel risk prediction models of breast cancer based on stanniocalcin-1 level.

The function of stanniocalcin-1 (STC-1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC-1 and prognosis in patients with breast cancer (BC) and to determine whether STC-1 could be a key prognostic factor in BC. The STC-1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C-index, and performing decision curve analyses (DCA). The level of STC-1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER-2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC-1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC-1 level were independent prognostic factors for distant disease-free survival (DDFS) and disease-free survival (DFS). Both the ROC curve and the C-index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. Nomograms were created based on STC-1 levels for 3-, 5-, and 7-year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC-1 level can be used clinically as a liquid biopsy indicator.

High expression COL10A1 promotes breast cancer progression and predicts poor prognosis

BackgroundAs a common malignant disease in females, breast cancer (BCa) causes increasing numbers of cancer-related death. Collagen X alpha 1 chain (COL10A1) plays a critical role in the oncogenesis and progression of malignant tumors. However, a systematic analysis of COL10A1 in BCa has not been conducted. MethodsThe COL10A1 expression level and prognostic value in BCa were defined through the Cancer Genome Atlas (TCGA) as well as the Kaplan-Meier plotter data respectively. The expression pattern of COL10A1 was subsequently confirmed on tissue microarray (TMA) by immunochemistry (IHC) staining. Moreover, cellular functional assays which aimed to evaluate cell proliferation, migration, invasion, and apoptosis, were conducted to investigate the oncogenic activity of COL10A1 in BCa. Then, Tumor Immune Estimation Resource (TIMER) was adopted to determine the association between COL10A1 expression and immune cell infiltration. ResultsBioinformatics analysis revealed that COL10A1 was significantly overexpressed and had notable prognostic value, especially for distant metastasis-free survival (DMFS) in BCa. Moreover, IHC analysis of 140 BCa tissues on TMA chips exhibited the overexpression of COL10A1 was correlated to advanced clinical stage, poor overall survival (OS), and worse recurrence-free survival (RFS). Besides, knockdown of COL10A1 remarkably suppressed cell proliferation, migration, and invasion in BCa cells, and notably promoted cell apoptosis as well. Furthermore, COL10A1 was positively associated with immune cell infiltration including B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell. ConclusionThe results revealed that COL10A1 is a novel oncogene and could serve as a potential prognostic biomarker in BCa. Besides, the downregulation of COL10A1 could inhibit BCa progression, which could be a potential target for BCa therapy.

Expression and Prognostic Value of Chromobox Family Proteins in Esophageal Cancer.

Background: Esophageal cancer (EC) is one of the most common human malignant tumors worldwide. Chromobox (CBX) family proteins are significant components of epigenetic regulatory complexes. It is reported that CBXs play critical roles in the oncogenesis and development of various tumors. Nonetheless, their functions and specific roles in EC remain vague and obscure. Methods and Materials: We used multiple bioinformatics tools, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, Kaplan–Meier plotter, cBioPortal, Metascape, TIMER2 and TISIDB, to investigate the expression profile, gene alterations and prognostic roles of CBX family proteins, as well as their association with clinicopathologic parameters, immune cells and immune regulators. In addition, RT-qPCR, Western blot, CCK8, colony formation, wound healing and transwell assays were performed to investigate the biological functions of CBX3 in EC cells. Results: CBX3 and CBX5 were overexpressed in EC compared to normal tissues. Survival analysis revealed that high expression of CBX1 predicted worse disease-free survival (DFS) in EC patients. Functionally, CBXs might participate in mismatch repair, spliceosome, cell cycle, the Fanconi anemia pathway, tight junction, the mRNA surveillance pathway and the Hippo signaling pathway in EC development. Furthermore, CBXs were related to distinct immune cells infiltration and immune regulators. Additionally, depletion of CBX3 inhibited the proliferation, migration and invasion abilities of EC cells. Conclusions: Our study comprehensively investigated the expression pattern, prognostic value, and gene alterations of CBXs in EC, as well as their relationships with clinicopathologic variables, immune cells infiltration and immune regulators. These results suggested that CBX family proteins, especially CBX3, might be potential biomarkers in the progression of EC.

The role of dual-specificity phosphatase 3 in melanocytic oncogenesis.

Dual-specificity phosphatase 3 (DUSP3), also known as Vaccinia H1-related phosphatase, is a protein tyrosine phosphatase that typically performs its major role in the regulation of multiple cellular functions through the dephosphorylation of its diverse and constantly expanding range of substrates. Many of the substrates described so far as well as alterations in the expression or the activity of DUSP3 itself are associated with the development and progression of various types of neoplasms, indicating that DUSP3 may be an important player in oncogenesis and a promising therapeutic target. This review focuses exclusively on DUSP3's contribution to either benign or malignant melanocytic oncogenesis, as many of the established culprit pathways and mechanisms constitute DUSP3's regulatory targets, attempting to synthesize the current knowledge on the matter. The spectrum of the DUSP3 interactions analysed in this review covers substrates implicated in cellular growth, cell cycle, proliferation, survival, apoptosis, genomic stability/repair, adhesion and migration of tumor melanocytes. Furthermore, the speculations raised, based on the evidence to date, may be considered a fundament for potential research regarding the oncogenesis, evolution, management and therapeutics of melanocytic tumors.

DIPG-28. IndolentH3 K27M-mutant diffuse midline glioma

Abstract INTRODUCTION: H3 K27M-mutant diffuse midline glioma (DMG) is an aggressive central nervous system tumor that is universally fatal with a median survival of 8-12 months after diagnosis. Here we present a patient who was incidentally found to have a lesion within the right thalamus on brain magnetic resonance imaging (MRI). Twelve years later, she was found to have a brain mass within the same area with pathology consistent with an H3 K27M-mutant DMG. CASE DESCRIPTION: A 14-year-old female presented with new onset left-sided numbness and weakness, blurry vision and a right-sided temporal headache. Her past medical history is significant for severe persistent asthma and anoxic brain injury secondary to a cardiopulmonary arrest at 2-years-of-age due to an asthma exacerbation. She has had multiple MRIs of her brain since her initial insult which initially showed the presence of a T2/FLAIR hyper-intense lesion within the right medial thalamus in addition to chronic central nervous system changes. The right thalamic lesion was stable in size between images obtained at 2-years and 4-years of age. Her current physical exam is significant for decreased strength to her left upper and lower extremities. Brain MRI with and without contrast is obtained with partial effacement of the third ventricle due to mass effect from an enlarging mass from the right thalamus. Biopsy of the lesion demonstrated an H3 K27M-mutant DMG, WHO grade IV. Our patient went on to receive palliative radiation therapy with 59.4 Gy over 33 fractions. DISCUSSION: This case illustrates an unusual presentation of an H3 K27M-mutant DMG with an indolent course, diagnosed twelve years after the initial MRI finding. This proposes the possibility of multiple factors playing a role in the oncogenesis of these aggressive tumors and that further research is warranted.