Molecular Characteristics Research Articles

The impact of integrated genomic analysis on molecular classifications and prognostic risk stratification in endometrial cancer: a Chinese experience

BackgroundThe molecular classification of endometrial cancer (EC), as proposed by The Cancer Genome Atlas (TCGA), has transformed tumor classification, but there is a lack of extensive research on the molecular profiles and subtyping of endometrial cancer patients in China.Methods200 EC patients were classified into the following four molecular types: (i) POLEmut; (ii) MSI-H; (iii) TP53mut; (iv) NSMP. This study aimed to investigate the molecular characteristics of EC patients at a single center by large-scale next generation sequencing(NGS), including clinicopathological features and gene mutations in patients with distinct molecular types, and to assess the relevance of molecular subtyping for postoperative adjuvant therapy.ResultsNSMP group was the most prevalent, comprising 46.0% (92/200) of cases, followed by the TP53mut group at 17.5% (35/200), the MSI-H group at 23.5% (47/200), and the POLEmut group at 13.0% (26/200). CTNNB1 mutations were common in the POLEmut group but rare in the TP53mut group. With the application of the new European Society for Medical Oncology (ESMO) 2022 classification, 27 patients (14.1%) were reclassified. Concordance between the two classifications regarding postoperative risk was observed in 85.9% (165/192) of cases. Seven patients (3.6%) were downstaged, and twenty patients (10.4%) were upgraded. Additionally, the analysis revealed that eleven genes were significantly mutated in patients with lymphovascular space invasion (LVSI) compared to those without LVSI. Notably, NSD3 and POLD1 were highly mutated in patients with lymphatic metastasis compared to those without lymphatic metastasis. Conclusively, large-scale NGS has revolutionized EC management by facilitating rapid molecular subtype identification, guiding tailored adjuvant therapies, targeted treatments, and immunotherapies, and efficiently screening for Lynch syndrome, thereby significantly improving patient outcomes.

Right-Sided Versus Left-Sided Colon Cancer—A 5-Year Single-Center Observational Study

Background: Global colorectal cancer (CRC) incidence is significant, constituting 15% of all cancer cases with 1.4 million new diagnoses annually. Recent research suggests categorizing CRC into three clinical groups: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer, each with distinct embryological and molecular characteristics. Methods: A retrospective analysis of 189 patients (103 men, 86 women) undergoing surgery for RCC and LCC from January 2018 to December 2023 was performed. Results: LCC was a more common localization (98, 51.85%) than RCC (91, 48.15%). Patients with RCC were older than patients with LCC (70 (36–92, IQR 11) vs. 68 (38–84, IQR 12.5) years; p = 0.02). The duration of surgical procedure was comparable in both groups (225 (120–420, IQR 80) vs. 210 (105–505, IQR 85) minutes; p = 0.16). Complications occurred in 16 (17.58%) patients with RCC and in 15 (15.31%) patients with LCC (p = 0.72). One-year overall survival was 92.76% (SE 2.16%) (91.57% (SE 3.43%) in the RCC group and 93.99% (SE 2.61%) in the LCC group; p = 0.79). Conclusions: Colon cancer incidence is increasing globally due to economic and lifestyle factors. Our study reflects this trend, noting a rise in cases from 2018 to 2023. Despite several differences, overall survival rates do not significantly differ between RCC and LCC patients. Understanding clinical disparities is crucial for optimizing patient outcomes.

Molecular Epidemiology Clinical Manifestations, Decolonization Strategies, and Treatment Options of Methicillin-Resistant Staphylococcus aureus Infection in Neonates

Preterm and low-birth-weight neonates are particularly susceptible to methicillin-resistant Staphylococcus aureus (MRSA) colonization, whereas MRSA infection is associated with significant neonatal morbidity and mortality globally. The objective of our study was to examine the current body of knowledge about molecular traits, epidemiology, risk factors, clinical presentation, decolonization techniques, and available treatments for MRSA infection in neonates. MRSA strains that predominate in neonatal units, namely healthcare-associated (HA)-MRSA, differ from community-acquired (CA)-MRSA strains in molecular characteristics, toxin synthesis, including Panton-Valentine leukocidin, and resistance to antibiotics. Colonization with MRSA predisposes neonates to infection. The clinical impact of MRSA infection includes bacteremia, sepsis, pneumonia, endocarditis, osteomyelitis, septic arthritis, skin and soft tissue infections, and toxic shock syndrome. To reduce MRSA transmission, colonization, and infection, customized approaches are required, including continuous surveillance of MRSA epidemiology, new techniques for detecting MRSA resistance, and the application of basic preventive measures. Antimicrobial susceptibility monitoring is essential to identify the best empirical antimicrobial treatments. The growing antibiotic resistance of MRSA remains challenging, and vancomycin is still the best option. Further extensive research and surveillance are warranted to explore the genetic diversity and prevalence of MRSA.

Selection Pressure Regulates the Evolution-Structure-Function Paradigm of Monocyte Chemoattractant Protein Family.

Monocyte chemoattractant proteins (MCPs) are involved in monocyte trafficking during severe inflammation by modulating the chemokine-glycosaminoglycan-receptor signaling axis. MCPs comprise a family of four chemokines (CCL2, CCL7, CCL8, and CCL13/12) that exhibit differential expression patterns in mammals, functional diversity, and receptor/glycosaminoglycan (GAG) binding promiscuity. In this context, the evolution-structure-function paradigm of MCP chemokines in mammals was established by assessing phylogeny, functional divergence, selection pressure, and coevolution in correlation with structural and surface characteristics. Comprehensive analyses were performed using an array of evolutionary and structural bioinformatic methods including molecular dynamics simulations. Our findings demonstrate that substitutions in receptor/GAG-interacting residues mediate episodic diversification and functional diversity in MCP chemokines. Additionally, a balanced interplay of selection pressures has driven the functional changes observed among MCP paralogs, with positive selection at various receptor/GAG-binding sites contributing to their promiscuous receptor/GAG interactions. Meanwhile, processes like purifying selection and coevolution maintain the classical chemokine structure and preserve the ancestral functions of MCP chemokines. Overall, this study suggests that selection pressure on sites within the N-terminal region [N-loop and 310-helix] and 40S loop of MCP chemokines alters surface properties to fine-tune the molecular interactions and functional characteristics without altering the overall chemokine structure.

Patient-Derived Meningioma Organoids: A Reliable Model for Studying Human Tumor Pathophysiology

Introduction: Meningiomas are the most common primary central nervous system tumors, constituting 39.7% of intracranial tumors. Although generally benign, some exhibit aggressive behavior and risk of recurrence, necessitating adjuvant therapy and repeat surgical interventions. Molecular studies have identified tumor-driving mutations, leading to targeted therapies and clinical trials. However, translating preclinical findings into clinical success is often hindered by limitations in current meningioma tumor models. This study aims to develop and validate a standardized protocol for establishing patient-derived meningioma organoids (MEN-Os) that faithfully replicate human disease. Methods: MEN-Os were successfully established from 15 meningioma samples (11 grade 1, 4 grade 2) from neurosurgical resections using an optimized culture protocol. Histological and immunohistochemical analyses were used to assess the resemblance of MEN-Os to original tumor tissues. RNA sequencing compared transcriptional signatures between MEN-Os and corresponding patient-resected tissues. Results: MEN-Os were successfully established from patient-resected samples and maintained in culture for up to four weeks, showing stable growth and structural integrity. Histopathological analysis revealed that MEN-Os preserved key architectural features, including cellular organization, nuclear morphology, and proliferation rates. Immunohistochemical staining for meningioma-specific markers, such as the progesterone receptor, confirmed similar expression patterns to parental tumors. Transcriptomic profiling demonstrated that MEN-Os retained the transcriptional signatures of original tissues, including genes associated with meningioma pathology (NF2, CDKN2A, TP53). Differential expression and deconvolution analyses showed that MEN-Os contained diverse cell populations, including tumor and stromal cells, while preserving the immune microenvironment, as validated by histopathological and transcriptomic profiling. Conclusion: We established a robust, reproducible protocol for generating MEN-Os, which faithfully replicates the histopathological, molecular, and cellular characteristics of original tumors. MEN-Os provide a valuable model for studying meningioma biology and evaluating therapeutic strategies.

Existence of Pentatrichomonas hominis in Tibetan Antelope (Pantholops hodgsonii)

IntroductionPentatrichomonas hominis is a conditional pathogen that parasitizes the intestines of vertebrates and has been detected in various wild animals. However, its infection rate in Tibetan antelopes has not been previously studied.MethodsIn this study, 503 fecal samples from Tibetan antelopes were analyzed to determine the prevalence and molecular characteristics of P. hominis.ResultsResults showed that 1.19% (6/503) of the samples tested positive, and although the prevalence was low, this finding underscores the importance of monitoring wild animals population as hosts of zoonotic pathogens. Additionally, the highest prevalence in Nima County (6.25%, 4/64), followed by Shenza County (2.44%, 2/82). No P. hominis was detected in samples from Shuanghu, Ruoqiang, Qiemo, and Qumarlêb Counties. Seasonally, the highest prevalence was recorded in autumn (1.42%, 6/423). Interestingly, P. hominis was only detected in 2020 (2%, 6/300), with no infections found in 2023 (0/50) or 2024 (0/153). Additionally, the phylogenetic analysis indicated that most islolates belonged to the CC1 genotype, with one representing a potential novel genotype.DiscussionThis is the first s to report the presence of P. hominis in Tibetan antelopes, revealing that Tibetan antelopes may be a potential transmitter of zoontic P. hominis. These findings offer new insights into its epidemiology and contribute valuable data for Tibetan antelope conservation efforts.

Antimicrobial Resistance in Pasteurella multocida Isolates from Bovine Mastitis Can Be Associated with Multidrug-Resistance-Mediating Integrative and Conjugative Elements (ICEs)

Background/Objectives: Pasteurella multocida commonly colonizes the bovine respiratory tract and can occasionally cause intramammary infections. Here, eight P. multocida isolates from clinical cases of bovine mastitis were investigated for their molecular characteristics as well as phenotypic and genotypic antimicrobial resistance (AMR) properties. Methods: The isolates originated from quarter milk samples obtained in Germany for diagnostic purposes. Antimicrobial susceptibility testing (AST) by broth microdilution was performed according to the Clinical and Laboratory Standards Institute. Closed whole-genome sequences were generated by hybrid assembly of Illumina MiSeq short-reads and Oxford Nanopore MinION long-reads, followed by consecutive sequence analysis. Results: The P. multocida isolates belonged either to capsular:lipopolysaccharide type A:3 (n = 7) or A:6 (n = 1), and multi-locus sequence types 1 (n = 7) or 7 (n = 1). Seven isolates carried AMR genes, such as mef(C), mph(G), strA, strB, aphA1, aadA31, tet(H), tet(Y), floR, catA3, and sul2, as part of an integrative and conjugative element (ICE). These mobile genetic elements, 58,382–78,401 bp in size, were highly similar to the ICEs Tn7406 or Tn7407 that have been previously described in bovine Mannheimia haemolytica and P. multocida, respectively. Moreover, the isolates showed elevated minimal inhibitory concentrations corresponding to the identified AMR determinants. Conclusions: Molecular typing and ICE organization suggest the bovine respiratory tract as reservoir of the investigated mastitis-associated P. multocida. Horizontal cross-genus transfer of multidrug-resistance-mediating ICEs seems to occur under in vivo conditions among different pathogens from cattle in Germany, which underlines the importance of pathogen identification followed by AST for successful bovine mastitis therapy.

Pulmonary Nuclear protein in Testis (NUT) carcinoma: clinical, molecular characteristics, and treatment strategies

BackgroundPulmonary nuclear protein in testis (NUT) carcinoma is a rare and aggressive malignancy that often exhibits clinical and pathological features overlapping with other thoracic malignancies, posing significant challenges for accurate diagnosis and leading to poor treatment outcomes.MethodWe conducted a retrospective analysis of five patients diagnosed with pulmonary NUT carcinoma between 2020 and 2023. Comprehensive clinical, imaging, histopathological, and molecular data and survival outcomes were collected.ResultsThe cohort included three females and two males, with a median age of 44 years. Clinical features commonly involved centrally located masses with mediastinal invasion. Distant metastases to bones, pleura, and lungs were confirmed in 60% of cases. Diagnostic confirmation was achieved through NUT protein positivity via IHC and FISH rearrangements in all five patients. RNA sequencing identified BRD3-NUTM1 fusions in 60% (3/5) patients. Chemotherapy was employed as the initial treatment strategy but showed limited efficacy in advanced stages. Among two patients undergoing surgical resection, better outcomes were achieved in the patient receiving adjuvant therapy with overall survival (OS) exceeding 36 months. Immunotherapy demonstrated limited benefit, likely attributable to low PD-L1 expression and an immunologically “cold” tumor microenvironment. Despite multimodal treatment approaches, three out of five patients in advanced pulmonary NUT carcinoma died to the disease, with OS ranging from 6 to 15 months.ConclusionAdvanced molecular techniques are critical for diagnosing pulmonary NUT carcinoma, but survival outcomes remain poor. Surgical resection with adjuvant therapy offers better outcomes for early-stage patients, while chemotherapy and immunotherapy show limited efficacy in metastatic cases due to the tumor’s aggressive behavior. Early detection and innovative therapies are essential for improving outcomes.

First Report of Leaf Tip Necrosis of Camellia oleifera Caused by Nigrospora aurantiaca in China.

In recent years, Camellia oleifera C.Abel. has become one of the most important woody oil trees cultivated at a large scale in Guizhou Province, China. However, the leaf diseases limited the development of C. oleifera industry. In October 2023, typical symptoms of leaf tip necrosis were observed on leaves of C. oleifera (Changlin series) at a plantation in Dongfeng Forest Farm (109°10'28'E, 26°18'41'N), Liping County, with disease incidence of 30-40% (n=220) in the observed fields (30 m × 30 m). The brown lesion started from the leaf tips, gradually extended inward then turned gray-white, curled, withered and fell off, and the boundary between the diseased and healthy parts was obvious. Symptomatic leaves (n=20) were collected and surface disinfected with 2% NaClO for 30 s, rinsed three times in sterile distilled water, air-dried and placed on potato dextrose agar (PDA) medium and incubated at 25°C for 7 d. The fungal colonies of 6 isolates were initially white, with red pigment, and later gradually turned gray, eventually turning black. Conidia were globose to sub-globose, black, smooth, single-celled, discrete and solitary, measuring 5.1 µm±1.28×4.7 µm±1.24 (n=50). The morphological features of the isolates are similar to the description of Nigrospora (Wang et al. 2017). For molecular identification, DNA of the representative isolate LP1021 was extracted using a fungal genomic DNA extraction kit (Sangon, Shanghai, China). The rDNA internal transcribed spacer (ITS), translation elongation factor 1-α (TEF-1α) and β-tubulin (TUB2) were amplified with the primers ITS1/ITS4 (White et al.1990), EF1-728F/EF1-986R (Carbone and Kohn, 1999) and Bt2a/Bt2b (Glass and Donaldson, 1995). The sequences of ITS, TEF-1α and TUB2 were deposited in GenBank as accession numbers PP499217, PP529954, and PP529955, respectively. BLAST revealed that ITS, TEF-1a and TUB2 sequences showed 100%, 98.80% and 100% similarity to those of N. aurantiaca (NR153477.1, KY019295.1 and MK388225.1), respectively. The phylogenetic tree constructed with the software MEGA X using the Neighbor-Joining algorithm (Felsenstein, 1985) indicated the isolate LP1021 separated from N. chinensis previously reported from C. oleifera in China. Based on morphological and molecular characteristics, the fungal pathogen was identified as N. aurantiaca. A representative isolate LP1021 was deposited in the Forest Protection Laboratory, Guizhou University. To further confirm the pathogenicity, a conidial suspension (1×104 spores/mL) of the isolate LP1021 was sprayed on six pots of two-year-old healthy C. oleifera seedlings in vivo. The same amounts of seedlings were sprayed with distilled water as control. All plants were placed at a constant room temperature of 25 ± 2°C. After 15 d, the inoculated leaves showed typical symptoms, similar to those observed in the field, while the control remained healthy. The re-isolated fungal culture was identical to that originally obtained using the methods mentioned above, which fulfilled Koch's postulates. To the best of our knowledge, this is the first report of N. aurantiaca causing leaf tip necrosis of C. oleifera in China, which provides an important theoretical basis for the pathogen identification and scientific control strategies of leaf tip necrosis in C. oleifera.

FTIR Spectroscopic Analysis of Plant Proteins and Correlation with Functional Properties.

Development of plant-based products faces challenges like raw material standardization and time-consuming functionality measurements. Fourier Transform Infrared (FTIR) spectroscopy provides a quick, non-destructive way to analyze protein molecular characteristics. This study explored the classification capability of FTIR in analyzing five plant protein isolates-soy, mung bean, pea, fava bean, and lentil-and assessed its predictive ability for functional property measurement such as water absorption capacity (WAC), oil absorption capacity (OAC), Solubility (SOL), foaming, and emulsification. Functional properties were calculated using traditional methods of measurements. Principal Component Analysis (PCA) and Partial Least Square (PLS) Regression Analysis were used to study FTIR spectra and its correlation with functional properties. PCA revealed distinct clusters for each protein source based on their FTIR spectra, indicating molecular differences. WAC and OAC prediction models showed strong correlations, with prediction correlation coefficients (Rp) of more than 0.99 and cross-validation correlation coefficients (Rcv) ranging from 0.85 to 0.92. As sample size increases, SOL, emulsifying, and foaming properties display promising potential. Moreover, WAC and OAC predictions exhibited robust results with protein blends of various ratios. The expanded WAC model predicted with an Rp of 0.99 and an Rcv of 0.95, while the expanded OAC model had an Rp of 0.99 and an Rcv of 0.84. The results underscore FTIR has the potential to identify plant proteins aiding in raw material verification and quality control as well as being an alternative to analyzing functional properties of plant proteins.

Molecular analysis of AmpC-producing Escherichia coli isolated from pediatric patients.

AmpC-mediated cephalosporin resistance occurs in 1.0% to 3.3% of Escherichia coli isolates due to production of either plasmid-mediated AmpC (p-AmpC) or chromosomal AmpC (c-AmpC). Data on the prevalence and molecular characteristics of AmpC-producing E. coli in pediatric patients are limited. We analyzed E. coli clinical strains with resistance phenotype consistent with AmpC production isolated from patients at a pediatric hospital in Japan between 2015 and 2022. Sequence types, resistance genes, and relevant mutations were identified through whole genome sequencing. Promoter and attenuator regions of the chromosomal ampC gene were examined and the presence of plasmid-mediated ampC genes was determined. Among 2,081 E. coli strains, 80 (3.8%) from 27 patients demonstrated the AmpC phenotype. The median patient age was 55 months, with 92.6% having underlying diseases, mainly renal and urinary tract abnormalities. Of the 27 strains, p-AmpC was found in 9 strains including 6 strains belonging to ST131, while c-AmpC was identified in 18 strains including 9 ST73 strains and 4 ST12 strains. ST131 and ST73 were the major AmpC-E. coli lineages isolated from children with underlying diseases. Most ST131 strains harbored p-ampC, while all ST73 strains acquired cephalosporin resistance by c-AmpC production through promoter and attenuator mutations, suggesting the presence of both AmpC mechanisms in a lineage-specific manner in E. coli identified among hospitalized children.

Morphological and molecular characterization of avian trypanosomes in domestic chickens (Gallus gallus domesticus) in Southeast Asia and review of the parasite morphometry in different avian hosts

ABSTRACT Avian trypanosomiasis is caused by flagellate protists of the genus Trypanosoma (Trypanosomatidae, Kinetoplastida). These parasites are transmitted by various blood-sucking arthropods. While these parasites are generally considered to have low pathogenicity, certain species can induce clinical symptoms in susceptible birds. In this study, detail morphological and molecular characteristics of Trypanosoma species isolated from domestic chicken (Gallus gallus domesticus) in Northeastern Thailand were investigated. In total, 58 buffy coat blood films, 60 thin blood films of fresh blood and 60 partial DNA sequences were analysed. Subsequently, Trypanosoma avium and Trypanosoma calmettei, which are rarely reported species in poultry as well as Trypanosoma sp. were characterised. Additionally, we provided the details of reviewed information of the parasite morphometry in different avian hosts. Phylogenetic analysis identified the most closely related avian Trypanosoma lineages. This study reports T. avium in domestic chickens and along with molecular characterization of T. calmettei, which are rarely reported species. Buffy coat and nested-PCR diagnostic methods were nearly similar in terms of sensitivity for trypanosome diagnostics, and both methods were more sensitive in comparison to microscopic examination of thin blood films. Relatively cheap buffy coat method is helpful for screening of trypanosomes infection in poultry, particularly during rapid fieldwork. In parasitology research, buffy coat and nested-PCR diagnostics are worth combining with thin blood smear microscopic examination, which provides valuable information about non-deformed trypomastigotes that are essential for morphospecies identification.

A comprehensive analysis of molecular characteristics of hot and cold tumor of gastric cancer

BackgroundThe advent of immunotherapy has revolutionized the treatment paradigm for gastric cancer (GC), offering unprecedented clinical benefits. However, a detailed molecular characterization of the tumor immune microenvironment in GC is essential to further optimize these therapies and enhance their efficacy.MethodsConsensus clustering was utilized to classify GC patients into distinct immune states, followed by an in-depth analysis of differences in mutation profiles, copy number variations, and DNA methylation patterns. Weighted gene co-expression network analysis (WGCNA) and correlation analysis were applied to identify gene modules underlying the classification of immune “hot” and “cold” tumors. Subsequently, 101 machine learning algorithm combinations were employed to construct a prognostic model based on the identified gene modules. Single-cell analysis was conducted to investigate cellular interactions associated with the immune-determinant gene module. Finally, immunofluorescence staining for CD8, CD45, and CXCR4 was performed on human GC tissue samples.ResultsA total of 1,298 GC patients were included in this comprehensive analysis. For the first time, we identified and characterized immune “hot” and “cold” tumors in GC patients, revealing distinct molecular features associated with these tumor types. Immune “hot” tumor-related genes were identified, and their functional roles were validated through biological behavior analysis. A prognostic signature, termed the hot tumor top regulators (HTTR), was developed using 101 machine learning algorithm combinations. The HTTR signature emerged as an independent prognostic factor, effectively stratifying patients into low- and high-risk groups with significant differences in overall survival. High-risk groups demonstrated strong associations with immune checkpoint regulation, antigen presentation, and inhibitory pathways. Notably, single-cell analysis revealed that HTTR genes were highly active in CD8 + T cells, with the CXCL12-CXCR4 axis playing a critical role in mediating interactions between CD8 + T cells and endothelial cells.ConclusionIn conclusion, the HTTR signature served as a robust prognostic biomarker for GC patients and effectively identified those with immune “hot” tumors. This finding provided valuable insights into the molecular mechanisms of tumor immunity in GC, offering potential avenues for targeted therapeutic interventions.

Clinicopathological and molecular characterization of astrocytoma

IntroductionAstrocytoma is a rare tumour of the central nervous system that often manifests with non-specific clinical symptoms and lacks distinct histological features. There is a pressing need for further understanding of the clinicopathological and molecular characteristics of astrocytoma. Identifying mutant genes can aid in reliable and early diagnosis, as well as provide insights for the development of targeted therapies.MethodsThis study aims to investigate the clinicopathologic and molecular characteristics of astroblastoma. A total of four patients diagnosed with astroblastoma were included in the analysis. Clinical features, histological findings, and immunohistochemistry results were reviewed and analyzed. Genetic alterations were identified using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), followed by patient follow-up.ResultsThe study included four female patients, ranging in age from 8 to 44 years. One patient had a tumour in the right parietal lobe, while the other three had tumours in the spinal cord. Histology is usually characterized by pseudorosettes of astroblasts and hyalinization of blood vessels. These tumors showed a growth pattern similar to traditional intracranial astroblastoma, and the histological manifestations of the four patients were all high-grade, showing features of high-density areas of tumor cells or necrosis. Immunohistochemical staining revealed that all four patients expressed OLIG2, EMA, and vimentin, while three patients also expressed GFAP and S-100. The Ki-67 positivity index was approximately 15% in three cases and 10% in one case. Fluorescence in situ hybridization (FISH) using break-apart probes showed EWRS1 breaks in three patients and MN1 breaks in one. Further DNA or RNA-targeted biallelic sequencing identified an EWSR1(Exon1-7)-BEND2(Exon2-14) fusion in case 1, and an EWSR1(Exon1-7)-BEND2(Intergenic) fusion in case 2. In case 3, an EWSR1(Exon1-7)-NUDT10(Intergenic) fusion was present, and in case 4, an MN1(Exon1)-BEND2(Exon2) fusion was identified. The EWSR1-NUDT10 gene fusion is a new fusion type in astroblastoma. The patients were followed up for 76.5, 17.6, 33.7, and 61.3 months, respectively. Three cases experienced tumour recurrences at the spinal cord site, with multiple recurrences in case 4.DiscussionOur study unveiled the distinctive clinicopathological and molecular mutational characteristics of astrocytoma, while also identifying rare mutated genes. Additionally, the detection of MN1 or EWSR1 gene fusion through FISH or next-generation sequencing can provide valuable insights into the molecular mechanisms and aid in the differential diagnosis of astrocytoma.

Hiding in plain sight: NUT carcinoma is an unrecognized subtype of squamous cell carcinoma of the lungs and head and neck.

In the past two decades, treatment for non-small-cell lung cancers (NSCLCs) and head and neck squamous cell carcinoma (HNSCC) has advanced considerably, owing largely to the characterization of distinct oncological subtypes, the development of targeted therapies for each subtype and the advent of immunotherapy. Data emerging over the past two decades suggest that NUT carcinoma, a highly aggressive malignancy driven by a NUT fusion oncoprotein and arising in the lungs, head and neck, and rarely in other sites, is a squamous cell carcinoma (SCC) based on transcriptional, histopathological, cell-of-origin and molecular characteristics. NUT carcinoma has an estimated incidence of 1,400 cases per year in the United States, surpassing that of some rare NSCLC and HNSCC subtypes. However, NUT carcinoma is currently not recognized as an SCC of the lungs or head and neck. The orphan classification of NUT carcinoma as a distinct entity leads to a lack of awareness of this malignancy among oncologists and surgeons, despite early diagnosis being crucial for this cancer type with a median survival of only ~6.5 months. Consequently, NUT carcinoma is underdiagnosed and often misdiagnosed, resulting in limited research and progress in developing effective treatments in one of the most aggressive forms of lung and head and neck cancer. With a growing number of targeted agents that can potentially be used to treat NUT carcinoma, improved recognition through reclassification and inclusion of NUT carcinoma as a squamous NSCLC or an HNSCC when arising in these locations will accelerate the development of effective therapies for this disease. Thus, in the Perspective, we propose such a reclassification of NUT carcinoma as an SCC and discuss the supporting evidence.

Lesion Conspicuity in Contrast-Enhanced Mammography: A Retrospective Analysis of Tumor Characteristics

Background/Objectives: The aim of this study is to evaluate the impact of tumor characteristics on lesion conspicuity in contrast-enhanced mammography (CEM) and identify factors associated with different levels of conspicuity. Methods: In this retrospective study, we analyzed 552 patients with breast cancer who underwent CEM. Lesion conspicuity was categorized into three levels: 1 (low), 2 (moderate), and 3 (high). Tumor characteristics included age, histological subtype, hormone receptor status, HER2 status, Ki67 index, tumor grade, and molecular subtype. Univariate and multivariate analyses were conducted to assess associations between lesion conspicuity and these factors. Results: Of the 552 cases, the majority showed mass enhancement (78.1%), followed by non-mass enhancement (NME) (16.8%), and a combination of mass and NME (4.0%). Lesion conspicuity was significantly associated with enhancement type on CEM (p < 0.001). High conspicuity (score 3) was predominantly observed in masses (84.8%) compared to NME (7.6%). Larger tumor dimensions (median 20 mm) were also associated with higher conspicuity (p < 0.001). Molecular subtypes differed significantly in conspicuity, with Luminal A tumors showing lower conspicuity compared to HER2-positive and triple-negative breast cancers (p = 0.025). In multivariate analysis, lesion conspicuity was strongly associated with enhancement type (p < 0.001) and tumor dimensions (p < 0.001), while histological subtype and molecular characteristics had no significant independent impact. Conclusions: Lesion conspicuity in CEM is primarily influenced by the type of enhancement and tumor size. Mass-forming lesions, particularly larger ones, are more conspicuous, while NME tends to result in lower conspicuity. These findings suggest that enhancement patterns and tumor dimensions are key factors to consider when interpreting CEM in breast cancer diagnosis.

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated the role of epigenetic modifications in the pathogenesis of breast cancer, including drug resistance and efflux characteristics, offering potential new diagnostic and prognostic markers, treatment efficacy predictors, and therapeutic agents. Key modifications include DNA cytosine methylation and the covalent modification of histone proteins. Unlike genetic mutations, reprogramming the epigenetic landscape of the cancer epigenome is a promising targeted therapy for the treatment and reversal of drug resistance. Epidrugs, which target DNA methylation and histone modifications, can provide novel options for the treatment of breast cancer by reversing the acquired resistance to treatment. Currently, the most promising approach involves combination therapies consisting of epidrugs with immune checkpoint inhibitors. This review examines the aberrant epigenetic regulation of breast cancer initiation and progression, focusing on modifications related to estrogen signaling, drug resistance, cancer progression, and the epithelial–mesenchymal transition (EMT). It examines existing epigenetic drugs for treating breast cancer, including agents that modify DNA, inhibitors of histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone demethyltransferases. It also delves into ongoing studies on combining epidrugs with other therapies and addresses the upcoming obstacles in this field.

Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization

PurposeThe 2021 WHO classification of central nervous system tumors introduced molecular criteria to stratify Grade 4 gliomas, which remain heterogeneous. This study aims to elucidate the clinical, radiological, and molecular characteristics of WHO Grade 4 gliomas, focusing on their prognostic implications and the development of a predictive model for astrocytoma IDH-mutant WHO Grade 4 (A4).MethodsA retrospective cohort of 223 patients from Beijing Tiantan Hospital was analyzed. Clinical, radiological, and histopathological data were combined with molecular profiling, focusing on IDH mutations, TERT promoter mutations, and MGMT methylation. A predictive model was developed using LASSO regression to distinguish A4 from glioblastomas and validated with an external dataset from UCSF.ResultsThe cohort included 201 glioblastomas (90.1%) and 22 A4 cases (9.9%). A4 tumors were associated with younger age, higher MGMT promoter methylation, lower rates of TERT mutations, and distinct radiological features, such as cortical non-enhancing tumor infiltration (CnCE). Patients with A4 demonstrated significantly better survival outcomes compared to glioblastoma patients (p < 0.001). The predictive model for A4, incorporating age, tumor margin, and CnCE, achieved an AUC of 0.890 in the training set and 0.951 in the validation set.ConclusionIntegrating molecular and clinical criteria improves prognostication in Grade 4 gliomas. The predictive model developed in this study effectively identifies A4 tumors, facilitating more personalized therapeutic strategies.

Association ana­lysis of the molecular characteristics and floral traits of Iris × germanica

Association ana­lysis of the molecular characteristics and floral traits of Iris × germanica

Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism.

The investigation into risk factors, molecular epidemiology, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in pediatric populations in China is currently inadequate. To assess epidemiology, molecular characteristics, and resistance mechanisms, virulence-associated genes were analyzed, alongside multi locus sequence typing (MLST), PCR, and qRT-PCR. Multivariate analysis identified prolonged hospitalization (OR: 1.026; 95 % CI: 1.004-1.049; P = 0.023) and increased exposure to enzyme inhibitor complex preparations (OR: 3.165; 95 % confidence interval [CI]: 1.113-8.999; P = 0.031) as independent risk factors for CRPA healthcare-associated infections (HAIs). Mortality rates were significantly higher in the HAI group compared to the non-HAI group (19.1 % vs. 6.0 %, P = 0.021). Analysis of virulence-associated gene combinations revealed 10 and 15 distinct profiles among HAI and non-HAI isolates, respectively, characterized by exoS-/exoU+ or exoS+ /exoU- genotypes, with no isolates exhibiting both exoS+ and exoU+ genotypes concurrently. Infections predominantly correlated with CC244, with a significantly greater occurrence in the HAI group (72.1 % vs. 46.3 %, P = 0.002). Antimicrobial susceptibility testing identified that both CC244 + and HAI isolates demonstrated elevated resistance across all tested antibiotics. Furthermore, low oprD expression was observed in 77.9 % of HAI isolates and 67.2 % of non-HAI isolates, while increased ampC production and mexB gene overexpression were infrequently detected (all P > 0.05). Prolonged hospital stays and an increased exposure to enzyme-inhibitor complex therapies were identified as independent risk factors for CRPA HAIs. CRPA demonstrated considerable genetic diversity, with STs predominantly represented by CC244, and virulence-associated genes have spread. The primary mechanism driving carbapenem resistance involved the downregulation of outer membrane porin protein oprD, accompanied by oprD mutation inactivation.