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Genomics Jun 2024Cynanchum thesioides, a xerophytic species utilized both as a medicinal herb and a food source, plays a significant role in arid and desert ecosystem management. Its...
Cynanchum thesioides, a xerophytic species utilized both as a medicinal herb and a food source, plays a significant role in arid and desert ecosystem management. Its inflorescence is an umbellate cyme, each carrying nearly a thousand flowers; however, its fruiting rate remains remarkably low. The normal development of the anther is a necessary prerequisite for plants to produce seeds. However, our understanding of the anther development process in Cynanchum thesioides remains limited. To better understand the pollen development process in Cynanchum thesioides, the stages of pollen development were determined through paraffin sectioning, and observations were made on the distribution characteristics of polysaccharides and lipid droplets in the pollen development of Cynanchum thesioides using Periodic Acid-Schiff stain (PAS) and 0.5% Sudan Black B tissue staining. Concurrently, the gene expression patterns and metabolite profiles were delineated across various developmental stages of Cynanchum thesioides anthers (T1: microspore stage, T2: tetrad stage, T3: mononuclear stage, and T4: maturation stage). The findings revealed that Cynanchum thesioides pollen is in an aggregate form. Polysaccharides gradually accumulate during maturation and lipid droplets form a surrounding membrane, thereby preventing pollen dispersion. Furthermore, transcriptomic and metabolomic analyses across distinct developmental phases uncovered a plethora of differentially expressed genes and metabolites associated with the flavonoid biosynthesis pathway. Flavonoid levels exhibited dynamic changes concurrent with anther development, aligning with the gene regulatory patterns of the corresponding biosynthetic pathways. The study identified 63 differentially accumulated flavonoid compounds and 21 differentially expressed genes associated with flavonoid biosynthesis. Weighted gene co-expression network analysis revealed six MYB and ten bHLH transcription factors as key candidates involved in flavonoid biosynthesis, with CtbHLH (Cluster-6587.1050) and CtMYB (Cluster-6587.31743) specifically regulating structural genes within the pathway. These findings underscore the pivotal role of flavonoid biosynthesis in anther development of Cynanchum thesioides. In conclusion, this research offers a comprehensive insight into the anther development process in Cynanchum thesioides.
PubMed: 38878835
DOI: 10.1016/j.ygeno.2024.110884 -
Journal of Translational Medicine Jun 2024Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for...
BACKGROUND
Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions.
METHODS
A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts.
RESULTS
The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis.
CONCLUSIONS
In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes.
Topics: Humans; Carcinoma, Renal Cell; Deep Learning; Kidney Neoplasms; Lymphatic Metastasis; Middle Aged; Male; Female; Prognosis; Cohort Studies; Image Processing, Computer-Assisted; Aged; Area Under Curve
PubMed: 38877591
DOI: 10.1186/s12967-024-05382-6 -
Laboratory Animal Research Jun 2024Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment...
BACKGROUND
Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment (TME). We aimed to build a multiplex immunofluorescence (mIF) panel to apply to formalin-fixed and paraffin-embedded tissues in mice tumors and to explore the programmed cell death protein 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis.
RESULTS
An automated eight-color mIF panel was evaluated to study the TME using seven antibodies, including cytokeratin 19, CD3e, CD8a, CD4, PD-1, PD-L1, F4-80 and DAPI, then was applied in six mice lung adenocarcinoma samples. Cell phenotypes were quantified by software to explore the co-localization and spatial distribution between immune cells within the TME. This mice panel was successfully optimized and applied to a small cohort of mice lung adenocarcinoma cases. Image analysis showed a sparse degree of immune cell expression pattern in this cohort. From the spatial analysis we found that T cells and macrophages expressing PD-L1 were close to the malignant cells and other immune cells.
CONCLUSIONS
Comprehensive immune profiling using mIF in translational studies improves our ability to correlate the PD-1/PD-L1 axis and spatial distribution of lymphocytes and macrophages in mouse lung cancer cells to provide new cues for immunotherapy, that can be translated to human tumors for cancer intervention.
PubMed: 38877529
DOI: 10.1186/s42826-024-00210-w -
Cancer Control : Journal of the Moffitt... 2024The present study aimed to evaluate the frequencies of , and mutations and their possible associations with clinicopathological features in 249 Moroccan patients with...
OBJECTIVES
The present study aimed to evaluate the frequencies of , and mutations and their possible associations with clinicopathological features in 249 Moroccan patients with colorectal cancer (CRC).
METHODS
A retrospective investigation of a cohort of formalin-fixed paraffin-embedded tissues of 249 patients with CRC was screened for // mutations using Idylla™ technology and pyrosequencing.
RESULTS
, and mutations were revealed in 46.6% (116/249), 5.6% (14/249), and 2.4% (6/249) of patients. exon 2 mutations were identified in 87.9% of patients (102/116). G12D and G12 C were the most frequent, at 32.8% and 12.93%, respectively. Among the patients with exon 2 wild-type (wt), 27.6% (32/116) harbored additional mutations. Concurrent mutations were identified in 9.5% (11/116); including six in codon 146 (A146P/T/V), three in codon 61 (Q61H/L/R), one in codon 12 (G12 A and Q61H), and one in codon 13 (G13D and Q61 L). Among the exon 2 wt patients, 64.3% (9/14) harbored additional mutations. Concurrent mutations were identified in 28.6% (4/14) of -mutant patients. Since 3.2% wt were identified with mutations, concomitant and mutations were identified in 2.4% (6/249) of patients. mutations were higher in the >50-year-old age-group ( = .031), and the tumor location was revealed to be significantly associated with mutations ( = .028) predominantly in left colon (27.5%) and colon (42.2%) locations. mutations were most prevalent in the left colon (42.8%) and in well-differentiated tumors (64.2%).
CONCLUSION
Detection of mutations, particularly the G12 C subtype, may be significant for patients with CRC and has possible therapeutic implications. However, rare concomitant mutations in CRC patients suggest that each individual may present distinct therapeutic responses. testing alongside the identification of other affected genes in the same patient will make the treatments even more personalized by contributing more accurately to the clinical decision process. Overall, early diagnosis using novel molecular techniques may improve the management of CRC by providing the most efficient therapies for Moroccan patients.
Topics: Humans; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Male; Female; Proto-Oncogene Proteins p21(ras); Membrane Proteins; Middle Aged; GTP Phosphohydrolases; Morocco; Mutation; Retrospective Studies; Aged; Adult; Aged, 80 and over; DNA Mutational Analysis
PubMed: 38875469
DOI: 10.1177/10732748241262179 -
Global Medical Genetics Jun 2024Anaplastic lymphoma kinase ( ) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to...
Anaplastic lymphoma kinase ( ) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of fusion-positive and fusion-negative in a large cohort of NSCLC patients. The formalin-fixed paraffin-embedded specimens of NSCLC patients who underwent next-generation sequencing from 2020 to 2023 in Yinfeng Gene Technology Co., Ltd. Clinical laboratory were included in this study. In the current study, a total of 180 (3.20%) patients tested positive for fusions in 5,622 NSCLC samples. Within the -positive cohort, a total of 228 fusions were identified. Furthermore, five novel fusion partners, including , , , , and were identified. In cases with fusion-positive, alterations were the most prevalent (26.3%), followed by (8.4%), epidermal growth factor receptor ( , 5.6%), and (5.6%). By contrast, alterations were most prevalent (51%) in patients with fusion-negative NSCLC, followed by (42.7%), (11.6%), and (11.3%). A total of 10 cases where fusion co-occurred with mutations were also identified. Notably, the fusion positivity rate was higher in younger patients ( < 0.0001) and in female patients ( = 0.0429). Additionally, positive test results were more prevalent in patients with high programmed death-ligand 1 expression, especially when applying a 50% cutoff. Collectively, these findings offer valuable genomic insights that could inform the personalized clinical care of patients with NSCLC harboring fusions within the context of precision medicine.
PubMed: 38873557
DOI: 10.1055/s-0044-1787301 -
Scientific Reports Jun 2024The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with...
The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood.
Topics: Humans; Stomach Neoplasms; DNA Copy Number Variations; Paraffin Embedding; Male; Female; High-Throughput Nucleotide Sequencing; Aged; Mutation
PubMed: 38871991
DOI: 10.1038/s41598-024-64541-3 -
Oral Surgery, Oral Medicine, Oral... Mar 2024This study aimed to analyze the clinicoradiologic features and Ki-67 proliferation indices between the histopathologic variants of ameloblastomas (ABs) for possible...
OBJECTIVES
This study aimed to analyze the clinicoradiologic features and Ki-67 proliferation indices between the histopathologic variants of ameloblastomas (ABs) for possible associations.
STUDY DESIGN
The diagnosis and histopathologic variant were confirmed for all cases by experienced Oral and Maxillofacial Pathologists. Immunohistochemistry for Ki-67 was performed on the most representative formalin-fixed paraffin-embedded tissue block. Demographic, clinical data and radiologic features were analyzed from patient records and available radiographic examinations. The investigators were blinded to the histopathologic variant and proliferation index when the clinicoradiologic features were assessed.
RESULTS
The current study included 116 cases of AB in the final sample. The indolent behavior of the unicystic variant was supported by their low proliferation index and slow growth paired with low frequencies of cortical destruction, loss of teeth, root resorption, and encroachment on anatomical structures. In contrast, the comparatively high proliferation index of the plexiform variant correlated with their fast growth and pain. Furthermore, high radiologic frequencies of cortical destruction, loss of teeth, and encroachment of surrounding anatomical structures supported their more aggressive clinical course.
CONCLUSION
Statistically significant differences were noted between certain variants and Ki-67, location, borders, locularity, and cortical destruction, providing better insight into their biological behavior.
PubMed: 38871622
DOI: 10.1016/j.oooo.2024.03.007