Development Of Malignant Tumors Research Articles

LncRNA DDX11-AS1 promotes breast cancer progression by targeting the miR-30c-5p/MTDH axis.

Long noncoding RNAs (lncRNAs) play a significant role in the occurrence and development of malignant tumours. However, ceRNAs, which are significantly associated with the prognosis of breast cancer (BC), need to be further investigated. Therefore, the current study aimed to investigate the effect of the lncRNA DDX11-AS1 on BC progression. Bioinformatics analysis via a public microarray revealed that DDX11-AS1 was upregulated in BC. The above findings were verified via RT‒qPCR analysis of BC tissues. Additionally, our study revealed that the expression levels of DDX11-AS1 increased with increasing pathological grade and lymph node metastasis. Furthermore, DDX11-AS1 knockdown markedly inhibited the proliferation, migration and invasion abilities of BC cells. Mechanistically, DDX11-AS1 could prevent the degradation of MTDH in BC via competitively binding with miR-30c-5p, which could act as a tumour promoter factor. Additionally, miR-30c-5p was downregulated and MTDH was upregulated in BC cells and tissues. The promoting effect of DDX11-AS1 on BC cells was enhanced by miR-30c-5p silencing and reduced by treatment with MTDH inhibitors. Collectively, the above results suggest that the DDX11-AS1/miR-30c-5p/MTDH axis could be associated with the progression of BC and that DDX11-AS1 could be a potential biomarker and therapeutic target for BC.

Whole-body MRI-based long-term evaluation of pediatric NF1 patients without initial tumor burden with evidence of newly developed peripheral nerve sheath tumors

BackgroundPatients with neurofibromatosis type 1 (NF1) can develop plexiform neurofibromas (PN). Large tumor burden is a predictor for the development of malignant peripheral nerve sheath tumors. Whole-body magnetic resonance imaging (WB-MRI) is the recommended imaging method for the evaluation of PN. WB-MRI is recommended for NF1 patients at transition from adolescence to adulthood. In the absence of internal PN further follow-up WB-MRI is not considered necessary. PN are often detected in early childhood, leading to the assumption that they may be congenital lesions. It remains unclear whether this invariably applies to all patients or whether patients who initially displayed no tumors can still develop PN over time. Therefore, we retrospectively reviewed WB-MRI scans of pediatric patients with NF1 without initial tumor burden and compared these with long-term follow-up scans for presence of newly developed PN.MethodsWe retrospectively reviewed WB-MRI scans of 17 NF1-children (twelve male; median age at initial scan: 9 [IQR 6.1–11.9] years) who initially displayed no PN. MRI scans with a follow-up interval of at least 6 years (median follow-up interval: 9 [IQR 5.6–12.4] years) were reviewed in consensus by two radiologists regarding the development of new PN over time.ResultsNew PN were identified in two out of 17 children without initial tumor burden in follow-up examinations. One of these two patients developed two larger distinct PN of 4.5 cm on the right upper arm and of 2.5 cm on the left thoracic wall between the age of ten and twelve. The second child developed multiple smaller PN along the major peripheral nerves between the age of eleven and 16. In addition, 15 of the children without initial tumor burden did not develop any distinct tumors for a period of at least 6 years.ConclusionOur results indicate that PN can be newly detected in pediatric patients over time, even if no PN were detected on initial MRI scans. Therefore, it seems reasonable to perform at least a second MRI in pediatric NF1 patients at transition to adulthood, even if they did not display any tumor burden on initial MRI, and when the MRI was performed significantly under the age of 18. With this approach, tumors that may have developed between scans can be detected and patients at risk for complications can be identified.

Research progress of organic small probes sensitive to tumor microenvironment

The development, metastasis, and spread of malignant tumors are closely associated with the inherent properties of tumor cells. These tumors often exhibit low pH, low polarity, high viscosity, and hypoxia. Understanding these characteristics is essential for early cancer detection and monitoring treatment effectiveness. Small molecule fluorescent probes have emerged as powerful tools for real-time localization, dynamic detection, and visualization of tumors. In this paper, we review recent progress in the use of these probes to study tumor biology, focusing on their design strategies, response mechanisms, and preclinical applications for detecting pH, viscosity, polarity, and hypoxia.

Comprehensive multi-omics analysis identifies chromatin regulator-related signatures and TFF1 as a therapeutic target in lung adenocarcinoma through a 429-combination machine learning approach

IntroductionLung cancer is a leading cause of cancer-related deaths, with its incidence continuing to rise. Chromatin remodeling, a crucial process in gene expression regulation, plays a significant role in the development and progression of malignant tumors. However, the role of chromatin regulators (CRs) in lung adenocarcinoma (LUAD) remains underexplored.MethodsThis study developed a chromatin regulator-related signature (CRRS) using a 429-combination machine learning approach to predict survival outcomes in LUAD patients. The CRRS model was validated across multiple independent datasets. We also investigated the impact of CRRS on the immune microenvironment, focusing on immune cell infiltration. To identify potential therapeutic targets, TFF1, a chromatin regulator, was knocked down using siRNA in LUAD cells. We assessed its impact through apoptosis analysis, proliferation assays, and in vivo tumor growth studies. Additional validation was performed using Ki67 expression and TUNEL assays.ResultsThe CRRS accurately predicted survival outcomes and was shown to modulate immune cell infiltration in the tumor microenvironment. High-risk patients demonstrated increased activity in cell cycle regulation and DNA repair pathways, along with distinct mutation profiles and immune responses compared to low-risk patients. TFF1 emerged as a key therapeutic target. Knockdown of TFF1 significantly inhibited LUAD cell proliferation, induced apoptosis, and suppressed in vivo tumor growth. Ki67 and TUNEL assays confirmed the role of TFF1 in regulating tumor growth and cell death.DiscussionThese findings highlight the potential of chromatin regulators in prognostic modeling and immune modulation in LUAD. TFF1 was identified as a promising therapeutic target, suggesting that targeting TFF1 could provide new treatment strategies. Further research is warranted to explore its full potential and therapeutic applicability.

Epithelial membrane protein 1 in human cancer: a potential diagnostic biomarker and therapeutic target.

Epithelial membrane protein 1 (EMP1) is a member of the small hydrophobic membrane protein subfamily. EMP1 is aberrantly expressed in various tumor tissues and governs multiple cellular behaviors (e.g., proliferation, differentiation, and migration). The resultant regulation of the cancer pathway is responsible for the metastasis of cancer cells and determines the risk of malignant tumor progression. This review provides an updated overview of EMP1 as either an oncogene or a tumor suppressor contingent on the cancer type and summarizes its upstream regulators and downstream target genes. This systematic review summarizes our current understanding of the role of EMP1 in malignant tumor development, including critical functional mechanisms and implications for its potential use as the biomarker and therapeutic target.

Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors.

Background: Neurofibromatosis type 1 (NF1) is a common inherited neurological disorder that can lead to the development of malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive form of sarcoma. Current treatment options for MPNSTs are limited, with poor prognosis and high recurrence rates. This study aims to explore the potential of targeting the Galectin-1 (Gal-1) and Ras interaction as a novel therapeutic strategy for MPNSTs. Methods: Molecular docking simulations were conducted to identify specific residues involved in the Gal-1 and H-Ras(G12V) interaction. LLS30, a compound designed to target the Ras binding pocket on Gal-1, was developed and tested. The efficacy of LLS30 was evaluated through in vitro assays, including cell viability, apoptosis, and co-immunoprecipitation studies, as well as in vivo assays using orthotopic MPNST xenograft and experimental lung metastasis models. Transcriptome sequencing was performed to analyze the impact of LLS30 on gene expression and signaling pathways. Results: Molecular docking revealed key residues involved in the Gal-1/Ras interaction, and LLS30 was shown to bind to these residues, disrupting the interaction. LLS30 treatment resulted in Ras delocalization from the plasma membrane and suppression of the Ras/Erk signaling pathway. In vitro, LLS30 significantly reduced MPNST cell proliferation and induced apoptosis. In vivo, LLS30 demonstrated potent anti-tumor activity, reducing tumor burden and metastasis while improving survival in animal models. Transcriptome analysis showed that LLS30 downregulates critical pathways, including KRAS signaling and epithelial-mesenchymal transition (EMT). Conclusions: Interference with the Gal-1/Ras interaction could lead to suppression of the Ras signaling pathway. LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.

MicroRNA-582-5p inhibits the progression of gastric cancer cells and their resistance to oxaliplatin by suppressing ATG7 expression.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract worldwide. Both environmental and genetic factors contribute to the occurrence and development of GC. Surgery and chemotherapy are the main treatment modalities for gastric cancer; however, some patients show insensitivity to chemotherapeutic agents. Chemotherapy resistance is one of the primary reasons for poor treatment outcomes and the high likelihood of recurrence and metastasis in gastric cancer patients. Numerous studies have confirmed a correlation between the dysregulation of microRNA expression and the development of various malignant tumors, as well as their resistance to chemotherapeutic agents. However, the role of microRNA-582-3p in gastric cancer cells and its mechanism in the resistance of gastric cancer cells to oxaliplatin have not been studied. We first used q-PCR, CCK8, transwell, and scratch assays to validate the expression of microRNA-582-3p in gastric cancer tissues and cells, while also analyzing the relationship between its expression levels and the clinical pathological data of patients. Additionally, we further confirmed the impact of microRNA-582-3p on gastric cancer cell progression and oxaliplatin resistance through knockdown and overexpression experiments. Subsequently, to explore the specific mechanisms of microRNA-582-3p in gastric cancer, we verified the downstream target of microRNA-582-3p, ATG7, using dual-luciferase reporter assays and examined the effect of ATG7 on gastric cancer cell functions. Moreover, we conducted rescue experiments to further validate the interaction between microRNA-582-3p and ATG7. Our experimental results confirmed that microRNA-582-3p is lowly expressed in gastric cancer tissues and cells, and the expression level of miR-582-5p is correlated with the T stage of patients, while showing no correlation with the patients' gender, age, tumor size, degree of differentiation, or N stage. Additionally, we found that microRNA-582-3p functions as a tumor suppressor in gastric cancer cells, as its overexpression inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin. Furthermore, we identified binding sites between microRNA-582-3p and the autophagy-related gene ATG7, observing that knockdown of microRNA-582-3p increases ATG7 expression, while its overexpression reduces ATG7 levels. Moreover, ATG7 is overexpressed in gastric cancer cells; knockdown of ATG7 inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin, whereas overexpression of ATG7 reverses the inhibitory effect of miR-582-5p on gastric cancer. Our study confirms that microRNA-582-3p acts as a tumor suppressor in gastric cancer cells, and its role may be mediated through the regulation of ATG7 expression levels. MicroRNA-582-3p may serve as a potential target for gastric cancer treatment and a predictive biomarker.

Immunological tolerance in breast cancer: some reasons for development

Immunological tolerance is one of the reasons for the development and progression of malignant tumors. The tumor immune cycle regulates the normal antitumor immune response, and it’s disruption is responsible for the development of immunological tolerance. This article provides a review of russian and foreign literature published in databases such as PubMed, Medline, and Cochrane, eLibrary in the last 5 years, focusing on the emergence of immunological tolerance in breast cancer from the perspective of disrupted regulation of tumor immune cycle phases: expression of antigens on the surface of tumor cells, cancer antigen presentation, priming and activation T cells, immune infiltration of the tumor site, recognition, and elimination of tumor cells. Understanding the mechanisms underlying tumor immune cycle disruption is important for identifying new immunopathogenetic links in the development of breast cancer, as well as identifying targets to improve the effectiveness of therapy for advanced breast cancer.

The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.

Short-chain fatty acids (SCFAs), which are saturated fatty acids consisting of six or fewer carbon atoms, have been found to be closely associated with the biological behavior of malignant tumors. This manuscript provides a comprehensive review on the role of SCFAs in regulating cell cycle, apoptosis, tumor angiogenesis, epithelial-mesenchymal transition, protein regulatory pathways, and histone regulation in promoting the development of malignant tumors. Furthermore, we discuss the potential therapeutic strategies targeting SCFAs for treating malignant tumors. This review offers a theoretical foundation for investigating the mechanisms by which SCFAs impact malignant tumors and provides insights into developing novel treatment targets.

Changes in electrical parameters of the heart in an experimental model of malignant tumor growth during of hyperthyroidism

Experimental and clinical studies demonstrate the possibility of modulating the development of malignant tumors in thyroid imbalance, in particular hyperthyroidism, which negatively affects the electrophysiology of the heart. In an experimental model of tumor growth during of hyperthyroidism, activation of the tumor was shown.Aim: To study electrophysiological parameters of the mouse heart at the initial stages of transplantable tumor growth during of hyperthyroidism.Material and Methods. In female mice of the C57BL/6 line (n = 20) was created a model of melanoma B16/F10 growth during of hyperthyroidism, which was induced by daily intraperitoneal administration of liothyronine sodium (T3) for a long time and confirmed by determining the content of thyroid-stimulating hormone and triiodothyronine in the blood using the radioimmune method. On the 5th day of T3 administration, the melanoma was transplanted. ECG was recorded non-invasively (ecgTUN- NEL, ecgAVG software, emka TECHNOLOGIES, France) on the 1st and 3rd days of T3 administration, in groups with a tumor – on the 6th day after its transplantation.Results. Pathological changes were revealed: in the group with hyperthyroidism – rhythm irregularity, decrease the amplitude of P and T below the isoline, widening of the QRS, on the 3rd day – the death of 1 mouse was noted due to large-focal myocardial infarction; in the group with melanoma – only sinus arrhythmia and decreased heart rate; in the group with a combination of pathologies – an almost normal ECG, with the exception of an increase in P amplitude and a slight increase in QRS.Conclusion. Already in the early stages of hyperthyroidism or tumor growth, there was a violation of myocardial depolarization/ repolarization processes, capable of causing even death of the animal. In case of comorbidity, the majority of ECG parameters normalized, indicating the inclusion of compensatory mechanisms in the interaction of pathologies. The results demonstrate the need for a deeper study of the mechanisms of interaction of several simultaneously existing pathologies in the body.

FBXO2 promotes the progression of papillary thyroid carcinoma through the p53 pathway

Emerging evidence have demonstrated that F-box only protein 2 (FBXO2) is intimately associated with malignant tumor development and occurrence. However, neither the functions nor the molecular mechanisms underlying FBXO2 have been determined in the papillary thyroid carcinoma (PTC). The quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry were carried out to detect the FBXO2 expression in PTC tissues. CCK-8 assay, EdU assay and flow cytometry were used to assess cell proliferation, cell cycle and apoptosis. The trans-well assay was conducted to determine the cell invasiveness. The effect of FBXO2 on PTC cell proliferation in vivo was observed through a subcutaneous tumor formation experiment in nude mice. Immunoprecipitation were conducted to detect the interaction between FBXO2 and p53. The ubiquitination assays were conducted to assess the regulation of p53 ubiquitination by FBXO2. FBXO2 was overexpressed in both PTC tissues and cell lines. FBXO2 expression positively correlated with PTC tumor size, lymphatic metastasis, and extramembranous invasion. Furthermore, silencing FBXO2 inhibited PTC cell proliferation and promoted apoptosis. The overexpression of FBXO2 significantly promotes PTC cell proliferation. Mechanistic studies revealed that FBXO2 could directly bind to p53 and promote its ubiquitination degradation. Knockdown of p53 partially reversed the progression arrest induced by FBXO2 Knockdown in PTC cells. FBXO2 knockdown inhibited PTC cell proliferation and promoted apoptosis by targeting p53 for ubiquitination and degradation. This process represents a research foundation for its diagnostic and therapeutic applications.

Exploring Novel Therapeutic Breakthroughs for Cancers: Potential Roles of miRNAs

MicroRNAs (miRNAs) are small non-coding RNAs, 19–25 nucleotides in length, that regulate gene expression. miRNAs are involved in various cellular, biological, and pathological activities, including the development and progression of malignant tumors. Numerous studies have highlighted the significant roles of miRNA deregulation in various cancer types, involving critical pathways such as gene deletions and amplifications, abnormal epigenetic changes, and dysfunctional miRNA regulatory systems. miRNAs can function both as oncogenes and tumor suppressor genes in different contexts. Several cancer hallmarks are associated with deregulated miRNAs, including resistance to cell death, metastasis, sustained proliferative signaling, promotion of angiogenesis, and the suppression of growth factors. Recent research has demonstrated that miRNAs contribute to drug resistance in tumor cells by targeting genes linked to drug resistance or by influencing genes that regulate the cell cycle, apoptosis, and proliferation. A single miRNA often has tissue-specific regulatory functions and can affect multiple genes. Various miRNA types have been identified as potential biomarkers for tumor diagnosis and critical targets for novel therapeutic approaches. This review aims to explore the role of miRNAs in cancer progression, metastasis, and potential therapeutic interventions.

Neurofibromatosis type 1: short review and clinical case

Neurofibromatosis type 1 (NF1) is acommon (1/3000) autosomal dominant disorder associated with amutation in the NF1 gene, located on the long arm of chromosome 17 (17q11.2). NF1 is diagnosed using well-known clinical criteria: café au lait spots, axillary and inguinal freckles, cutaneous and subcutaneous neurofibromas, optic pathway gliomas, and specific bone abnormalities. The pathognomonic feature of the disease is plexiform neurofibroma (PN), which is abenign peripheral nerve sheath tumor that occurs in 30-50% of patients with NF1. In addition to awide range of clinical manifestations, such as pain, motor, respiratory disorders, neurological deficits, cosmetic defects, etc., there is about a15% risk for the development of malignant peripheral nerve sheath tumors (MPNST). And it should be noted that the treatment of PN is acomplex task that does not have one standard solution. Thus, surgical treatment, which was the “gold standard” and remains one of the main methods of therapy, carries significant risks, such as postoperative neurological deficit, ahigh risk of intraoperative bleeding and is accompanied by ahigh percentage of relapses. Therefore, the emergence of targeted therapy and its use in the Russian Federation since 2021 has made asignificant contribution to the treatment of symptomatic inoperable plexiform neurofibromas.

Obesity and the Risk of Thyroid Cancer: A Literature Review

Introduction and aim of the study: Thyroid cancer is considered the most common endocrine malignant worldwide in recent years. Also, obesity has become a true pandemic. The correlation between the increase in cases of not only obesity but also thyroid cancer could not be explained solely by earlier and more meticulous cancer diagnoses. This study aims to review the literature on the relationship between obesity and the risk of thyroid cancer. Materials and Methods: The authors conducted a comprehensive review of the literature available in PubMed and Medline databases focusing on the terms "thyroid cancer" and "obesity". Results: Obesity is associated with a state of chronic inflammation and nonspecific activation of the immune system, leading to the production of cytokines and adipokines. These elements, through complex mechanisms, directly and indirectly promote carcinogenesis. Despite the association of excessive body weight with malignant tumor development, oncological treatment cannot rely solely on lifestyle changes and should be conducted precisely as it is for individuals with normal body weight. Another popular research topic in recent years has been circadian rhythm disorders. These disorders are confirmed to be a pro-carcinogenic factor but are also considered as an element that could accelerate diagnosis. Conclusions: Understanding the relationship between obesity and thyroid cancer, primarily molecular mechanisms is essential for developing effective preventive and therapeutic strategies to reduce the risk of thyroid cancer in obese patients.

Comprehensive Analysis of the Significance of Breast Cancer Gene 1 (BRCA-1) in Bladder Cancer.

Bladder carcinoma (BLCA) is characterized by high morbidity, mortality, and treatment costs. Breast cancer gene 1 (BRCA1), a tumor suppressor gene, inhibits the development of malignant tumors. However, research on the significance of BRCA1 in BLCA is limited. This study aims to explore the importance of BRCA1 in BLCA using bioinformatic methods and immunohistochemistry. Gene expression, clinical, and survival data were collected from the TCGA databases through the UCSC Xena platform (http://xena.ucsc.edu/). The TPM data from the TCGA and GETEx databases were integrated using the GEPIA database (http://GEPIA.cancer-pku.cn). The study then explored the differential expression, survival prognosis, functional enrichment, and immune cell infiltration analyses of BRCA1 in BLCA. A PPI network of BRCA1 was constructed using the STRING database, and a BRCA1-associated gene-gene interaction network was generated using the GeneMANIA database. Immunohistochemistry (IHC) assays were performed to verify the expression levels of BRCA1 in bladder tumour tissues and adjacent normal tissues. BRCA1 is associated with BLCA. Differential analysis indicated that BRCA1 acts as a risk factor for BLCA but does not show significant expression differences across genders, stages, tumor stages, lymph node stages, or metastasis stages. Additionally, staging was based on the eighth edition of the American Joint Committee on Cancer (AJCC) for BLCA. Co-expression network and Gene Set Enrichment Analysis (GESA) confirmed that BRCA1 is involved in various BLCA pathways. Furthermore, BRCA1 expression was also linked to immune cell infiltration. However, survival prognosis analysis revealed no significant correlation between the prognosis of BLCA and BRCA1. We demonstrated that BRCA1 is a prospective predicted and immunological biomarker in BLCA, offering new avenues for potential therapies.

Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma.

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.

Copy number variations contribute to malignant tumor development in children with serious birth defects.

There are two key signatures of pediatric cancers: (a) higher prevalence of germline alterations and (b) heterogeneity in alteration types. Recent population-based assessments have demonstrated that children with birth defects (BDs) are more likely to develop cancer even without chromosomal anomalies; therefore, explorations of genetic alterations in children with BDs and cancers could provide new insights into the underlying mechanisms for pediatric tumor development. We performed whole-genome sequencing (WGS) on blood-derived DNA for 1556 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumor, 757 cancer-free children with BDs, and 345 healthy individuals, focusing on copy number variation (CNV) analysis. Roughly half of the children with BD-cancer have CNVs that are not identified in BD-only/healthy individuals, and CNVs are not evenly distributed among these patients. Strong heterogeneity was observed, with a limited number of cancer predisposition genes containing CNVs in more than three patients. Moreover, functional enrichments of genes with CNVs showed that dozens of patients have variations related to the same biological pathways, such as deletions of genes with neurological functions and duplications of immune response genes. Phenotype clustering uncovered recurrences of patients with sarcoma: A notable enrichment was observed involving non-coding RNA regulators, showing strong signals related to growth and cancer regulations in functional analysis. In conclusion, we conducted one of the first genomic studies exploring the impact of CNVs on cancer development in children with BDs, unveiling new insights into the underlying biological processes.

An Immunohistochemical Study of MAGE Proteins in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one the most common primary malignancies with high mortality and morbidity. The melanoma-associated antigen (MAGE) gene family includes several genes that are highly expressed in numerous human cancers, making many of them part of the cancer-testis antigen (CTA) family. MAGE-C1 is expressed in various malignancies but is absent in normal cells, except for the male germ line. Its presence is associated with a worse prognosis, increased tumor aggressiveness, and lymph node invasion. Similarly, MAGE-C2 is linked to the development of various malignant tumors. Despite these associations, the roles and mechanisms of MAGE-C1/MAGE-C2 in HCC remain unclear. This study aimed to evaluate the expression of MAGE-C1 and MAGE-C2 in HCC and correlate it with clinicohistological characteristics. Our findings indicated that MAGE-C1 expression is associated with a higher number of nodules, elevated AFP levels, HBV or HCV positivity, older age, male sex, and lymph node invasion. MAGE-C2 expression was correlated with these characteristics and the presence of cirrhosis. These results align with the limited literature, which suggests a correlation between MAGE expression and older age and HBV infection. Consequently, our study suggests that MAGE-C1 and MAGE-C2 are promising novel biomarkers for prognosis and potential therapeutic targets in HCC.

Characterization of cuproptosis signature in clear cell renal cell carcinoma by single cell and spatial transcriptome analysis

Cuproptosis is a novel type to regulate cell death with copper-dependent manner, and has been reported to involve in the occurrence and development of various malignant tumors. However, the association between cuproptosis and the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remained unclear. To address this question, we integrated the single cell RNA sequencing (scRNA-seq) datasets of ccRCC across different stages, systematically examined the distinctive expression patterns of cuproptosis-related genes (CRGs) within the TME of ccRCC, and explored the crucial signatures using the spatial transcriptome sequencing (ST-seq) dataset. The cuproptosis activities reduced in cancer tissues along with the ccRCC development, and recovered after therapy. We identified HILPDA+ ccRCC1 subtype, characterized with hypoxia, as cuproptosis susceptible cells associated with a better prognosis. The main co-expression modules of HILPDA+ ccRCC1 subtype highlighted the role in anion transport, response to oxygen species and PD-L1-PD-1 pathway. Furthermore, the immunosuppressive cells might interact with HILPDA+ ccRCC1 subtype via HAVCR2-LGALS9, C3-C3AR1, HLA-A-CD8B and HLA-C-CD8A axises to shape the cuproptosis-related TME landscape. In summary, we anticipate that this study will offer valuable insights and potential strategies of cuproptosis for therapy of ccRCC.Graphical

Relationships of omega-3 and omega-6 polyunsaturated fatty acids with esophageal diseases: a two-sample Mendelian randomization analysis.

Omega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized. Mendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR-Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10-4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10-2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases. This study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.