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Croatian Medical Journal Jun 2024To determine variations in allele and genotype frequencies between keratoacanthoma (KA) and common warts (CW), compared with the control group, in three single...
AIM
To determine variations in allele and genotype frequencies between keratoacanthoma (KA) and common warts (CW), compared with the control group, in three single nucleotide polymorphisms (SNPs) within the TLR2, TLR3, and TLR9 genes.
METHODS
This case-control study involved samples from 161 patients with KA, 152 patients with CW, and 469 controls. DNA was isolated from formalin-fixed paraffin-embedded tissue sections. Three SNPs - rs4696480 in TLR2, rs7657186 in TLR9, and rs35213 in TLR3 - were genotyped with TaqMan Genotyping Assays on the 7500 Real-Time PCR System.
RESULTS
TLR2 rs4696480 and TLR3 rs7657186 were significantly overrepresented in KA and CW compared with controls (P<0.001). The association was stronger for CW than for KA, as evidenced by higher frequencies of the A allele and AA genotype for rs4696480. Both KA and CW patients had higher frequencies of the G allele and GG genotype for rs7657186 than controls. rs7657186 was moderately associated with KA and CW, with the G allele and GG genotype being more prevalent in CW cases, where no AA homozygotes were found.
CONCLUSION
Genetic variants in TLR2 (rs4696480) and TLR3 (rs7657186) genes may affect KA and CW development, influencing immune responses and susceptibility to these skin lesions. Further research is required to elucidate TLR expression patterns and their role in KA development.
Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Young Adult; Alleles; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Genotype; Keratoacanthoma; Polymorphism, Single Nucleotide; Toll-Like Receptor 2; Toll-Like Receptor 3; Warts
PubMed: 38868969
DOI: 10.3325/cmj.2024.65.232 -
Scientific Reports Jun 2024Zinc finger MIZ-type containing 1 (ZMIZ1) is a transcriptional coactivator related to the protein inhibitors of activated STATs (PIAS) family. Mounting evidence suggests...
Zinc finger MIZ-type containing 1 (ZMIZ1) is a transcriptional coactivator related to the protein inhibitors of activated STATs (PIAS) family. Mounting evidence suggests that ZMIZ1 plays a crucial role in the occurrence and development of cancers. The function of ZMIZ1 in tongue squamous cell carcinoma (TSCC) and the mechanisms underpinning its role in this disease have not been fully clarified. We performed qualitative ZMIZ1 protein expression analyses using immunohistochemistry in 20 patient-derived, paraffin-embedded TSCC tissue sections. We used RNAi to knock down ZMIZ1 expression in the CAL-27 TSCC cell line and quantified the impact of ZMIZ1 knock down on proliferation, migration and apoptosis via CCK-8, scratch assay and flow cytometry, respectively. We used qRT-PCR and western blotting to investigate the role of ZMIZ1 in this cell line. Finally, we established a model of lung metastasis in nude mice to replicate the in vitro results. ZMIZ1 protein was significantly more abundant in TSCC case tissue samples. ZMIZ1 knockdown reduced the invasion and metastases of TSCC tumor cells and promoted apoptosis. ZMIZ1 knockdown was associated with the down-regulation of Notch signaling pathway related factors Jagged1 and Notch1, and invasion and metastasis related factors MKP-1, SSBP2 and MMP7 in vitro and in vivo, at the mRNA level. In vitro and in vivo data suggest that knock down of ZMIZ1 may inhibit TSCC invasion and metastasis by modulating Notch signaling. ZMIZ1 inhibition may therefore represent a new therapeutic target for TSCC.
Topics: Animals; Female; Humans; Male; Mice; Middle Aged; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Jagged-1 Protein; Lung Neoplasms; Mice, Nude; Receptor, Notch1; Signal Transduction; Tongue Neoplasms; Transcription Factors; Xenograft Model Antitumor Assays
PubMed: 38866828
DOI: 10.1038/s41598-024-59882-y -
Indian Journal of Pathology &... Jun 2024Rspondin 1 (Rspo1), a protein family member featuring secreted furin-like domains, plays a pivotal role in cancer development and exhibits a positive correlation with...
CONTEXT
Rspondin 1 (Rspo1), a protein family member featuring secreted furin-like domains, plays a pivotal role in cancer development and exhibits a positive correlation with tumor progression. However, its expression in esophageal squamous cell carcinoma (ESCC) is still unknown.
AIMS
Here, we assessed the correlation between Rspo1 and clinicopathological features of ESCC patients, and further investigated the potential role of Rspo1 in ESCC development and clinical outcomes.
SETTINGS AND DESIGN
This was a pilot study.
MATERIALS AND METHODS
A total of 112 paraffin-embedded tumor samples from patients with ESCC, including 68 matched adjacent normal tissues, were collected post-surgery. Subsequently, tissue microarray (TMA) and immunohistochemistry (IHC) techniques were employed to assess the protein levels of Rspo1.
STATISTICAL ANALYSIS
All statistical analyses were performed with SPSS 20.0 (SPSS, Inc., Chicago, IL).
RESULTS
We found that Rspo1 expression was significantly higher in ESCC than in adjacent normal tissues (P < 0.0001). Moreover, Rspo1 was highly expressed in ESCC tumor specimens and showed a significant correlation with the T classification of ESCC (P < 0.05). Additionally, our findings indicate a positive relationship between Rspo1 and survival time in ESCC. Patients exhibiting moderate to high levels of Rspo1 expression demonstrated superior survival outcomes compared to those with low expression (P = 0.0002).
CONCLUSIONS
Our investigation has demonstrated that Rspo1 is upregulated in ESCC and exhibits a positive correlation with disease progression. Furthermore, we have observed a significant association between Rspo1 overexpression and improved patient survival rates, indicating its potential as a prognostic marker and therapeutic target for ESCC treatment.
PubMed: 38864442
DOI: 10.4103/ijpm.ijpm_452_23 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Jun 2024To investigate the characteristics of the CD8 T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8 T cells...
OBJECTIVE
To investigate the characteristics of the CD8 T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8 T cells infiltration and prognosis, to study the function of C-X-C motif chemokine ligand 11 (CXCL11) and its receptor in CD8 T cells infiltration into tumors and to explore the potential mechanism, and to provide the necessary clinicopathological basis for exploring the immunotherapy of MB.
METHODS
In the study, 48 clinical MB samples (12 cases in each of 4 subtypes) were selected from the multiple medical center from 2012 to 2019. The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString PanCancer IO360 Panel (NanoString Technologies). Immunohistochemistry (IHC) staining of formalin-fixed, paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8 T cells in the MB four subtypes. Through bioinformatics analysis, the relationship between CD8T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated. The expression of CXCR3 receptor on the surface of CD8T cells in MB was verified by double immunofluorescence staining, and the underlying molecular mechanism of CD8T cells infiltration into the tumor was explored.
RESULTS
The characteristic index of CD8T cells in the WNT subtype of MB was relatively high, suggesting that the number of CD8T cells in the WNT subtype was significantly higher than that in the other three subtypes, which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus (GEO) database analysis by using R2 online data analysis platform. And the increase of CD8T cells infiltration was positively correlated with the patient survival. The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes. Immunofluorescence staining showed the presence of CXCL11 receptor, CXCR3, on the surface of CD8T cells, suggesting that the CD8T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.
CONCLUSION
The CD8T cells infiltrate more in the WNT subtype MB than other subtypes. The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system, and the patients with more infiltration of CD8T cells in tumor have better prognosis. This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8T cells infiltration in MB, and give a new potential therapeutic target for the future immunotherapy of MB.
Topics: Humans; CD8-Positive T-Lymphocytes; Medulloblastoma; Receptors, CXCR3; Chemokine CXCL11; Prognosis; Lymphocytes, Tumor-Infiltrating; Cerebellar Neoplasms; Male; Female
PubMed: 38864138
DOI: 10.19723/j.issn.1671-167X.2024.03.019 -
BMC Cancer Jun 2024Evaluation of human epidermal growth factor receptor 2 (HER2) overexpression caused by erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification (AMP) by...
BACKGROUND
Evaluation of human epidermal growth factor receptor 2 (HER2) overexpression caused by erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification (AMP) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is essential for treating unresectable metastatic gastric cancer (GC). A targeted tumour sequencing test enables comprehensive assessment of alterations in cancer-related genes, including ERBB2. This study aimed to evaluate the concordance between the targeted tumour sequencing test and IHC/FISH for detecting HER2-positive GC and to clarify the significance of ERBB2 AMP and concomitant genetic alterations in HER2 downstream pathways (DPs) in anti-HER2 therapy for unresectable metastatic GC patients.
METHODS
ERBB2 copy number alteration (CNA) was examined via a targeted tumour sequencing test in 152 formalin-fixed paraffin-embedded (FFPE) GC tissues. ERBB2 CNA was compared to HER2 status evaluated by IHC/FISH in FFPE block sections, which were identical to those subjected to the targeted tumour sequencing test. Treatment outcomes of anti-HER2 therapy in 11 patients with unresectable metastatic GC was evaluated.
RESULTS
ERBB2 AMP (≥ 2.5-fold change) was detected by the targeted tumour sequencing test in 15 patients (9.9%), and HER2 positivity (IHC 3 + or IHC 2+/FISH positive) was detected in 21 patients (13.8%). The overall percent agreement, positive percent agreement, negative percent agreement and Cohen's kappa between ERBB2 CNA and HER2 status were 94.7%, 66.7%, 99.2% and 0.75, respectively. Progression-free survival for trastuzumab therapy in patients with ERBB2 AMP was significantly longer than that in patients with no ERBB2 AMP detected by the targeted tumour sequencing test (median 14 months vs. 4 months, P = 0.007). Treatment response to trastuzumab therapy was reduced in patients with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs. One patient with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs achieved a durable response to trastuzumab deruxtecan as fourth-line therapy.
CONCLUSIONS
A targeted tumour sequencing test is a reliable modality for identifying HER2-positive GC. ERBB2 AMP and concomitant genetic alterations detected through the targeted tumour sequencing test are potential indicators of treatment response to trastuzumab therapy. The targeted tumour sequencing test has emerged as a plausible candidate for companion diagnostics to determine indications for anti-HER2 therapy in the era of precision medicine for GC.
Topics: Humans; Stomach Neoplasms; Receptor, ErbB-2; Female; Male; Gene Amplification; Aged; Middle Aged; In Situ Hybridization, Fluorescence; Adult; Aged, 80 and over; Immunohistochemistry; Trastuzumab; DNA Copy Number Variations; Biomarkers, Tumor
PubMed: 38862927
DOI: 10.1186/s12885-024-12482-5 -
Scientific Reports Jun 2024The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with...
The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.
Topics: Humans; Carcinoma, Renal Cell; Prognosis; Tumor Microenvironment; Kidney Neoplasms; Lymphocytes, Tumor-Infiltrating; Female; Male; Risk Assessment; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Middle Aged; Immunotherapy; Sulfonamides
PubMed: 38862642
DOI: 10.1038/s41598-024-64207-0 -
Anais Brasileiros de Dermatologia Jun 2024Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal...
BACKGROUND
Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF.
OBJECTIVES
To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF.
METHODS
Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database.
RESULTS
In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients.
STUDY LIMITATIONS
Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment.
CONCLUSION
The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.
PubMed: 38851894
DOI: 10.1016/j.abd.2023.11.006 -
Communications Biology Jun 2024Robotically assisted proteomics provides insights into the regulation of multiple proteins achieving excellent spatial resolution. However, developing an effective...
Robotically assisted proteomics provides insights into the regulation of multiple proteins achieving excellent spatial resolution. However, developing an effective method for spatially resolved quantitative proteomics of formalin fixed paraffin embedded tissue (FFPE) in an accessible and economical manner remains challenging. We introduce non-robotic In-insert FFPE proteomics approach, combining glass insert FFPE tissue processing with spatial quantitative data-independent mass spectrometry (DIA). In-insert approach identifies 450 proteins from a 5 µm thick breast FFPE tissue voxel with 50 µm lateral dimensions covering several tens of cells. Furthermore, In-insert approach associated a keratin series and moesin (MOES) with prolactin-induced protein (PIP) indicating their prolactin and/or estrogen regulation. Our data suggest that PIP is a spatial biomarker for hormonally triggered cytoskeletal remodeling, potentially useful for screening hormonally affected hotspots in breast tissue. In-insert proteomics represents an alternative FFPE processing method, requiring minimal laboratory equipment and skills to generate spatial proteotype repositories from FFPE tissue.
Topics: Humans; Proteomics; Paraffin Embedding; Cytoskeleton; Female; Biomarkers; Tissue Fixation; Prolactin; Formaldehyde; Intracellular Signaling Peptides and Proteins; Microfilament Proteins; Membrane Transport Proteins
PubMed: 38851810
DOI: 10.1038/s42003-024-06354-8 -
Brazilian Journal of Otorhinolaryngology Apr 2024Frozen biopsy may guide surgical intraoperative decisions. We evaluated the accuracy of frozen biopsy for diagnosing benign, dysplastic and malignant laryngeal lesions,...
OBJECTIVE
Frozen biopsy may guide surgical intraoperative decisions. We evaluated the accuracy of frozen biopsy for diagnosing benign, dysplastic and malignant laryngeal lesions, compared to paraffin section (gold standard).
METHODS
Retrospective review of the charts of all patients presenting with laryngeal lesions suspicious of malignancy, who underwent laryngeal microsurgery with frozen biopsy in our institution, between 2015 and 2020. Results of frozen biopsy and paraffin section examinations were compared.
RESULTS
Among 113 samples of 89 patients, paraffin section diagnosed 23 benign, 31 dysplastic and 59 malignant lesions. The accuracy of the frozen biopsy in identifying dysplasia or malignancy was 80.5% (91/113), and greater for lesions >5 mm (78.8% × 51.5%; p = 0.009). The positive and negative predictive values, sensitivity and specificity were 95.9%, 51.3%, 78.9% and 86.9%, respectively.
CONCLUSIONS
Frozen section is a reliable tool when malignancy is detected, but almost half of benign results exhibit dysplasia or malignancy in paraffin section. Other clinical parameters should be considered in intraoperative decisions to prevent undertreatment.
PubMed: 38848629
DOI: 10.1016/j.bjorl.2024.101434 -
Medicine Jun 2024To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum,... (Observational Study)
Observational Study
To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin βB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.
Topics: Humans; Male; Female; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Medicine, Chinese Traditional; Middle Aged; Retrospective Studies; Adult; DNA, Viral; Inhibins; Herpesvirus 4, Human; Biomarkers, Tumor; Neoplasm Staging; Inhibin-beta Subunits; Aged; Antigens, Viral; Immunoglobulin A; Capsid Proteins
PubMed: 38847724
DOI: 10.1097/MD.0000000000038416