Pathology oncology research : POR最新文献

{"title":"Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib.","authors":"Fangling Hu,&nbsp;Liang Guo,&nbsp;Jieqing Yu,&nbsp;Daofeng Dai,&nbsp;Yuanping Xiong,&nbsp;Yuanqiao He,&nbsp;Wensheng Zhou","doi":"10.3389/pore.2021.1610008","DOIUrl":"https://doi.org/10.3389/pore.2021.1610008","url":null,"abstract":"<p><p><b>Objective:</b> The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end. <b>Methods:</b> Fresh tumor tissues of HNSCC patients were screened in terms of <i>in vitro</i> drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib <i>in vivo</i>. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment <i>in vivo</i>. <b>Results:</b> Anlotinib suppressed the <i>in vitro</i> proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis. <b>Conclusion:</b> Anlotinib suppressed HNSCC growth <i>in vitro</i> and <i>in vivo</i> (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610008"},"PeriodicalIF":2.8,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer.","authors":"Jasiya Qadir,&nbsp;Sabhiya Majid,&nbsp;Mosin Saleem Khan,&nbsp;Fouzia Rashid,&nbsp;Mumtaz Din Wani,&nbsp;Showkat Ahmad Bhat","doi":"10.3389/pore.2021.1609826","DOIUrl":"https://doi.org/10.3389/pore.2021.1609826","url":null,"abstract":"<p><p>AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by <i>ARID1A</i>-deficient cancer cells exhibited elevated <i>PDL1</i> expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the <i>ARID1A</i> mutation and expression of <i>ARID1A</i>, <i>TP53</i> and <i>PDL1</i> genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of <i>ARID1A</i> gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the <i>ARID1A</i>, <i>TP53</i> and <i>PDL1</i> genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the <i>ARID1A, TP53</i> and <i>PDL1</i> gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of <i>ARID1A</i> and elevated mRNA expression of <i>TP53</i> and <i>PDL1</i> was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that <i>ARAD1A</i> under-expression and overexpression of <i>TP53</i> and <i>PDL1</i> might be crucial for tumor progression with <i>TP53</i> and <i>PDL1</i> acting synergistically.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609826"},"PeriodicalIF":2.8,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39738474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases.","authors":"Yuxiang Deng,&nbsp;Long Yu,&nbsp;Yujie Zhao,&nbsp;Jianhong Peng,&nbsp;Yanbo Xu,&nbsp;JiaYi Qin,&nbsp;Binyi Xiao,&nbsp;Songran Liu,&nbsp;Mei Li,&nbsp;Yujing Fang,&nbsp;Zhizhong Pan","doi":"10.3389/pore.2021.1610077","DOIUrl":"https://doi.org/10.3389/pore.2021.1610077","url":null,"abstract":"<p><p><b>Introduction:</b> Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs). <b>Methods:</b> One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored. <b>Results:</b> In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (<i>p</i> = 0.036 and <i>p</i> = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including \"Myc targets,\" \"E2F targets\" and \"DNA repair\" pathways. <b>Conclusion:</b> Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610077"},"PeriodicalIF":2.8,"publicationDate":"2021-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39738476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics.","authors":"Gyula Remenyi,&nbsp;Zsuzsanna Bereczky,&nbsp;Réka Gindele,&nbsp;Aniko Ujfalusi,&nbsp;Arpad Illes,&nbsp;Miklos Udvardy","doi":"10.3389/pore.2021.1609987","DOIUrl":"https://doi.org/10.3389/pore.2021.1609987","url":null,"abstract":"<p><p>Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline <i>VHL</i> mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. <i>VHL</i> polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for <i>VHL</i> mutations. There were no classical somatic <i>VHL</i> mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 <i>VHL</i> c.-195G>A polymorphism accompanied by erythrocytosis. These patients are <i>Jak-2</i> negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609987"},"PeriodicalIF":2.8,"publicationDate":"2021-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39719967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Diagnostic and Prognostic Biomarkers and Candidate Therapeutic Drugs of Gastric Cancer Based on Transcriptomics and Single-Cell Sequencing.","authors":"Xu Zhao,&nbsp;Shuang Wu,&nbsp;Jingjing Jing","doi":"10.3389/pore.2021.1609955","DOIUrl":"https://doi.org/10.3389/pore.2021.1609955","url":null,"abstract":"<p><p><b>Background and Objective:</b> Gastric cancer (GC) is an important health burden and the prognosis of GC is poor. We aimed to explore new diagnostic and prognostic indicators as well as potential therapeutic targets for GC in the current study. <b>Methods:</b> We screened the overlapped differentially expressed genes (DEGs) from GSE54129 and TCGA STAD datasets. Protein-protein interaction network analysis recognized the hub genes among the DEGs. The roles of these genes in diagnosis, prognosis, and their relationship with immune infiltrates and drug sensitivity of GC were analyzed using R studio. Finally, the clinically significant hub genes were verified using single-cell RNA sequencing (scRNA-seq) data. <b>Results:</b> A total of 222 overlapping genes were screened, which were enriched in extracellular matrix-related pathways. Further, 17 hub genes were identified, and our findings demonstrated that BGN, COMP, COL5A2, and SPARC might be important diagnostic and prognostic indicators of GC, which were also correlated with immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and sensitivity of therapeutic drugs. The scRNA-seq results further confirmed that all four hub genes were highly expressed in GC. <b>Conclusion:</b> Based on transcriptomics and single-cell sequencing, we identified four diagnostic and prognostic biomarkers of GC, including BGN, COMP, COL5A2, and SPARC, which can help predict drug sensitivity for GC as well.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609955"},"PeriodicalIF":2.8,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39719966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering a Key Role of ETS1 on Vascular Abnormality in Glioblastoma.","authors":"Jiefu Tang,&nbsp;Yaling Li,&nbsp;Boxuan Liu,&nbsp;Wei Liang,&nbsp;Sanbao Hu,&nbsp;Meilian Shi,&nbsp;Jie Zeng,&nbsp;Mingzhen Li,&nbsp;Minjiang Huang","doi":"10.3389/pore.2021.1609997","DOIUrl":"https://doi.org/10.3389/pore.2021.1609997","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive type of brain tumor. Microvascular proliferation and abnormal vasculature are the hallmarks of the GBM, aggravating disease progression and increasing patient morbidity. Here, we uncovered a key role of ETS1 on vascular abnormality in glioblastoma. ETS1 was upregulated in endothelial cells from human tumors compared to endothelial cells from paired control brain tissue. Knockdown of Ets1 in mouse brain endothelial cells inhibited cell migration and proliferation, and suppressed expression of genes associated with vascular abnormality in GBM. ETS1 upregulation in tumor ECs was dependent on TGFβ signaling, and targeting TGFβ signaling by inhibitor decreased tumor angiogenesis and vascular abnormality in CT-2A glioma model. Our results identified ETS1 as a key factor regulating tumor angiogenesis, and suggested that TGFβ inhibition may suppress the vascular abnormality driven by ETS1.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609997"},"PeriodicalIF":2.8,"publicationDate":"2021-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39806385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling Activins and Follistatin in Colorectal Cancer According to Clinical Stage, Tumour Sidedness and Smad4 Status.","authors":"Bassem Refaat,&nbsp;Jamal Zekri,&nbsp;Akhmed Aslam,&nbsp;Jawwad Ahmad,&nbsp;Mohammed A Baghdadi,&nbsp;Abdelrazak Meliti,&nbsp;Shakir Idris,&nbsp;Sufian Sultan,&nbsp;Hosam Alardati,&nbsp;Haitham Akram Saimeh,&nbsp;Aiman Alsaegh,&nbsp;Mai Alhadrami,&nbsp;Tahira Hamid,&nbsp;Mohammed E Naeem,&nbsp;Shereef Ahmed Elsamany","doi":"10.3389/pore.2021.1610032","DOIUrl":"https://doi.org/10.3389/pore.2021.1610032","url":null,"abstract":"<p><p>This study explored the roles of activins and follistatin in colorectal cancers. Paired malignant and normal colonic tissues were collected from archived paraffin-embedded (<i>n</i> = 90 patients) alongside fresh (<i>n</i> = 40 patients) specimen cohorts. Activin β-subunits, follistatin and Smad4 mRNAs and proteins were measured by real-time PCR and immunohistochemistry (IHC). Mature activin-A, -B, -AB and follistatin proteins were measured by ELISA. Cancer tissues having ≤ the 20th percentile of the Smad4 IHC score were considered as low (L-S4) group. The Smad4-intact SW480 and Smad4-null HT29 colon cancer cell lines were treated with activins and follistatin, and cell cycle was analysed by flow cytometry. The cell cycle inducing (CCND1/CCND3) and inhibitory (p21/p27) proteins alongside the survival (survivin/BCL2) and pro-apoptosis (Casp-8/Casp-3) markers were measured by immunofluorescence. Thirty-nine patients had right-sided cancers (30%) and showed higher rates of L-S4 tumours (<i>n</i> = 17; 13.1%) alongside worse clinicopathological characteristics relative to left-sided cancers. The βA-subunit and activin-A increased, whilst βB-subunit and activin-AB decreased, in malignant sites and the late-stage cancers revealed the greatest abnormalities. Interestingly, follistatin declined markedly in early-stage malignant tissues, whilst increased significantly in the advanced stages. All activin molecules were comparable between the early stage right- and left-sided tumours, whereas the late-stage right-sided cancers and L-S4 tumours showed more profound deregulations. <i>In vitro</i>, activin-A increased the numbers of the SW480 cells in sub-G1 and G0/G1-phases, whereas reduced the HT29 cell numbers in the sub-G1 phase with simultaneous increases in the G0/G1 and S phases. The p21/p27/Casp-8/Casp-3 proteins escalated, whilst CCND1/CCND3/BCL2/survivin declined in the SW480 cells following activin-A, whereas activin-A only promoted p21 and p27 alongside reduced CCND3 in the HT29 cells. By contrast, activin-AB increased the numbers of SW480 and HT29 cells in Sub-G1 and G0/G1-phases and promoted the anti-cancer and reduced the oncogenic proteins in both cell lines. In conclusion, activins and follistatin displayed stage-dependent dysregulations and were markedly altered during the advanced stages of right-sided and L-S4 cancers. Moreover, the activin-A actions in CRC could be Smad4-dependent, whereas activin-AB may act as a Smad4-independent tumour suppressor protein.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610032"},"PeriodicalIF":2.8,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39806386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC13A4 Might Serve as a Prognostic Biomarker and be Correlated with Immune Infiltration into Head and Neck Squamous Cell Carcinoma.","authors":"Meng-Ling Yang,&nbsp;Jia-Hua Zhang,&nbsp;Sheng Li,&nbsp;Rui Zhu,&nbsp;Li Wang","doi":"10.3389/pore.2021.1609967","DOIUrl":"https://doi.org/10.3389/pore.2021.1609967","url":null,"abstract":"<p><p>SLC13A4 is a sodium sulfate co-transporter, which is expressed in brains, placentas, thymes and other tissues, plays an essential role in maintaining the metabolic balance of sulfate <i>in vivo</i>. The TCGA database shows that it is differentially expressed in a variety of tumors, but its prognostic value in tumors has not been clarified. TCGA, Oncomine and Timer databases were used to analyze SLC13A4 mRNA expression in cancer tissues and normal tissues, and its correlation with clinical prognosis in head and neck tumor. The CIBERSORT database was used to analyze the correlation between SLC13A4 expression and the infiltration of immune cells. SLC13A4 enrichment analysis was carried out by GSEA. SLC13A4 mRNA levels were significantly lower in head and neck tumors than in paracancer tissues. SLC13A4 expression in Head and neck squamous cell carcinoma (HNSCC) was closely related to tumor pathological grade and clinical stage. Decreased SLC13A4 expression was associated with poor overall survival (OS), progression free survival (PFS), disease specific survival (DSS) and recurrence free survival (RFS) in HNSCC patients. The expression of SLC13A4 was negatively correlated with Monocytes, M1 macrophages, M2 macrophages, resting CD4+ memory T cells, resting NK cells and activated NK cells, but positively correlated with neutrophils, plasma cells, T follicular helper cells, gamma delta T cells, regulatory T cells and naive B cells. In addition, the genes in SLC13A4 low-expression group were mainly concentrated in immunity-related activities, viral diseases, typical tumor pathways and metabolism. The SLC13A4 high expression group was mainly enriched in metabolic pathways. These suggest that SLC13A4 may be a potential prognostic biomarker in HNSC and correlated with immune infiltrates.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609967"},"PeriodicalIF":2.8,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39673361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients.","authors":"Hai Cai,&nbsp;Hang Chen,&nbsp;Qi Huang,&nbsp;Jun-Ming Zhu,&nbsp;Zhi-Bin Ke,&nbsp;Yun-Zhi Lin,&nbsp;Qing-Shui Zheng,&nbsp;Yong Wei,&nbsp;Ning Xu,&nbsp;Xue-Yi Xue","doi":"10.3389/pore.2021.1609941","DOIUrl":"https://doi.org/10.3389/pore.2021.1609941","url":null,"abstract":"<p><p><b>Objective:</b> To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa). <b>Materials and Methods:</b> We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated. <b>Results:</b> A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients. <b>Conclusions:</b> This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1609941"},"PeriodicalIF":2.8,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39622737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features.","authors":"Sándor Turkevi-Nagy,&nbsp;Ágnes Báthori,&nbsp;János Böcz,&nbsp;László Krenács,&nbsp;Gábor Cserni,&nbsp;Bence Kővári","doi":"10.3389/pore.2021.1610039","DOIUrl":"https://doi.org/10.3389/pore.2021.1610039","url":null,"abstract":"<p><p><b>Introduction:</b> A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin. We assessed the applicability of two novel markers, syntaxin-1 and insulinoma-associated protein 1 (INSM1) in breast carcinomas. <b>Methods:</b> Hypercellular (Type B) mucinous carcinomas, solid papillary carcinomas, invasive carcinomas of no special type with neuroendocrine features and ductal carcinomas <i>in situ</i> of neuroendocrine subtype were included in our study. The immunohistochemical panel included chromogranin A, synaptophysin, CD56, syntaxin-1 and INSM1. The specificity of syntaxin-1 and INSM1 was determined using samples negative for chromogranin A, synaptophysin and CD56. <b>Results:</b> The sensitivity of syntaxin-1 was 84.7% (50/59), with diffuse positivity in more than 60% of the cases. Syntaxin-1 also had an excellent specificity (98.1%). Depending on the definition for positivity, the sensitivity of INSM1 was 89.8% (53/59) or 86.4% (51/59), its specificity being 57.4% or 88.9%. The sensitivities of chromogranin A, synaptophysin and CD56 were 98.3, 74.6 and 22.4%, respectively. <b>Discussion:</b> Syntaxin-1 and INSM1 are sensitive and specific markers of breast tumors with neuroendocrine features, outperforming chromogranin A and CD56. We recommend syntaxin-1 and INSM1 to be included in the routine neuroendocrine immunohistochemical panel.</p>","PeriodicalId":411887,"journal":{"name":"Pathology oncology research : POR","volume":" ","pages":"1610039"},"PeriodicalIF":2.8,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39613281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}