Pathology, research and practice最新文献

{"title":"PGP9.5 expression in human tumors: A tissue microarray study on 13,920 tumors from 120 different tumor entities","authors":"Sekander Scherzai ,&nbsp;Maximilian Lennartz ,&nbsp;Frank Jacobsen ,&nbsp;Florian Viehweger ,&nbsp;David Dum ,&nbsp;Anne Menz ,&nbsp;Ria Schlichter ,&nbsp;Andrea Hinsch ,&nbsp;Doris Höflmayer ,&nbsp;Claudia Hube-Magg ,&nbsp;Christoph Fraune ,&nbsp;Christian Bernreuther ,&nbsp;Patrick Lebok ,&nbsp;Sören Weidemann ,&nbsp;Guido Sauter ,&nbsp;Till S. Clauditz ,&nbsp;Till Krech ,&nbsp;Andreas H. Marx ,&nbsp;Ronald Simon ,&nbsp;Stefan Steurer ,&nbsp;Sarah Minner","doi":"10.1016/j.prp.2024.155676","DOIUrl":"10.1016/j.prp.2024.155676","url":null,"abstract":"<div><div>The protein gene product 9.5 (PGP9.5), also termed ubiquitin C-terminal hydrolase L1 (UCH-L1) is an important component of the ubiquitination/deubiquitination system and plays a role in axonal transport. To comprehensively determine PGP9.5 expression in neoplastic tissues, a tissue microarray containing 13,920 samples from 120 different tumor types and subtypes was analyzed by immunohistochemistry (IHC). PGP9.5 immunostaining was found in 109 of 120 tumor categories, 87 of which contained at least one strongly positive case. PGP9.5 positivity was most seen in neuronal and neuroendocrine neoplasms (50–100 %), germ cell neoplasms (28–84 %), sarcomas and carcinosarcomas (up to 91 %), and in mesotheliomas (58–83 %). In clear cell RCC (renal cell carcinomas), strong PGP9.5 staining was associated with high ISUP (International Society of Urological Pathology) grade (p&lt;0.0001), advanced pT stage (p=0.0003), nodal (p=0.0242) and distant metastasis (p&lt;0.0001) as well as with a short overall, tumor specific and recurrence free survival (p≤0.0007 each). In papillary RCC, strong PGP9.5 staining was associated with high ISUP grade (p=0.009) and reduced recurrence free survival (p=0.0221). In urothelial carcinoma of the urinary bladder, high PGP9.5 expression was associated with muscle-invasion (p&lt;0.0001). PGP9.5 immunostaining was unrelated to histological parameters for tumor aggressiveness in 295 serous high-grade ovarian carcinomas, 174 endometrioid endometrium carcinomas, 292 papillary and 89 follicular thyroid carcinomas, 405 ductal adenocarcinomas of the pancreas and in 327 gastric adenocarcinomas. In summary, our data provide a comprehensive overview of PGP9.5 expression in cancer and demonstrate positive cases in a broad range of entities. PGP9.5 overexpression is linked to patient outcome in some tumor entities (i.e., clear cell RCC) but appears to be unrelated to clinically relevant tumor characteristics in many other frequent tumor entities.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155676"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the diagnostic potential of SOCS3 in copper metabolism for acute myocardial infarction","authors":"Duixin Qiu,&nbsp;Xinrong Jia,&nbsp;Ye Ding,&nbsp;Yating Gao,&nbsp;Xiaodong Chen,&nbsp;Dan Huang","doi":"10.1016/j.prp.2024.155688","DOIUrl":"10.1016/j.prp.2024.155688","url":null,"abstract":"<div><div>Acute myocardial infarction (AMI) represents a critical cardiovascular condition necessitating rapid and precise diagnostic strategies. This study investigates the diagnostic implications of genes involved in copper metabolism homeostasis in AMI. We identified genes related to copper metabolism and AMI from Genecards and GEO databases, conducting differential gene analysis via R software. Gene function was annotated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, while the STRING database facilitated key gene identification via topological analysis. The diagnostic value of these genes, particularly cytokine signaling 3 (SOCS3), was assessed using ROC curve analysis. SOCS3 expression was validated using <em>in-vitro</em> and <em>in-vivo</em> models, including cardiomyocyte hypoxia/reoxygenation (H/R) and rat myocardial infarction (MI) model. Further, we examined the effects of SOCS3 knockout on cell proliferation, apoptosis, and myocardial infarction severity. 77 genes were identified, with 73 showing upregulation and 4 downregulation. These genes mainly participated in pathways related to cytokine activation, inflammation regulation, and lipid metabolism. Network analysis highlighted 10 key genes, with SOCS3 exhibiting significant diagnostic potential (AUC &gt; 0.9). Validation experiments confirmed SOCS3 overexpression in disease models, with its knockout leading to decreased apoptosis, reduced infarct size, and improved cardiac function. This study highlights the diagnostic relevance of genes associated with copper metabolism, particularly SOCS3, in AMI. These findings offer novel insights into the molecular mechanisms of AMI, supporting the development of targeted diagnostic and therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155688"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-glutamyl cyclotransferase, a molecule identified from the invasive front of follicular thyroid carcinoma, is useful for differential diagnosis of follicular thyroid tumors","authors":"Toshiyuki Mitsuhashi ,&nbsp;Sachiko Ogasawara ,&nbsp;Masamichi Nakayama ,&nbsp;Reiichiro Kondo ,&nbsp;Jun Akiba ,&nbsp;Kenta Murotani ,&nbsp;Takeharu Ono ,&nbsp;Fumihiko Sato ,&nbsp;Hirohito Umeno ,&nbsp;Hirohisa Yano","doi":"10.1016/j.prp.2024.155678","DOIUrl":"10.1016/j.prp.2024.155678","url":null,"abstract":"<div><div>We aimed to establish a useful molecular marker for differentiating between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). RNA was extracted from the invasive front and paired tumor center tissues from three FTC cases using laser microdissection for cDNA microarray analysis, revealing high expression of gamma-glutamyl cyclotransferase (GGCT) in the invasive front. Subsequently, immunohistochemical (IHC) staining of GGCT was performed with formalin-fixed paraffin-embedded (FFPE) sections of FTC (n = 32), FA (n = 64), and follicular tumor of uncertain malignant potential (FT-UMP, n = 5). The GGCT expression score (range: 0–300) was calculated by multiplying the intensity score (0–3) and percentage of positive cells. The Ki-67 labeling index was also assessed in 20 FTC and 25 FA cases from the same cohort. The GGCT expression score was higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, <em>P</em> &lt; 0.0001). With the GGCT expression score, using a cutoff value of 101.1, the differentiation between FTC and FA was possible with a sensitivity of 68.8 % and specificity of 87.5 % (AUC = 0.832). With the Ki-67 labeling index, applying a cutoff value of 4.0 %, the distinction between FTC and FA resulted in a sensitivity of 50.0 % and specificity of 80.0 % (AUC = 0.677). The GGCT expression score was positively related to the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, <em>P</em> = 0.0164). Therefore, GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may be indicative of its invasive and proliferative activity.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155678"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms and pathological implications of CYP24A1 in Vitamin D metabolism","authors":"KL Milan,&nbsp;K.M. Ramkumar","doi":"10.1016/j.prp.2024.155684","DOIUrl":"10.1016/j.prp.2024.155684","url":null,"abstract":"<div><div>CYP24A1 is a crucial gene within the cytochrome P450 superfamily, responsible for encoding the enzyme 25-hydroxyvitamin D3–24-hydroxylase. This enzyme is involved in the catabolism of 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D3, by hydroxylating its side chain. Through this process, CYP24A1 tightly regulates the bioavailability and physiological impact of vitamin D3 in the body. Dysregulation of CYP24A1, particularly its overexpression, has been increasingly associated with the progression of various diseases, including cancers, autoimmune disorders, and chronic inflammatory conditions. Elevated levels of CYP24A1 can lead to excessive degradation of vitamin D3, resulting in diminished levels of this critical hormone, which is essential for calcium homeostasis, immune function, and cellular proliferation. This review explores into the structural characteristics of CYP24A1, exploring how it influences its enzymatic activity. Furthermore, it examines the expression patterns of CYP24A1 across different diseases, emphasizing the enzyme's role in disease pathology. The review also discusses the regulatory mechanisms governing CYP24A1 expression, including genetic mutations, epigenetic modifications, and metabolite-mediated regulation. By understanding these mechanisms, the review provides insight into the potential therapeutic strategies that could target CYP24A1, aiming to alleviate its overexpression and restore vitamin D3 balance in disease states.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155684"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subclinical amyloid deposition in inflammatory bowel diseases: A two hospital study","authors":"Yuichiro Hamamoto ,&nbsp;Kansuke Kido ,&nbsp;Michihiro Kawamura ,&nbsp;Yuki Sekido ,&nbsp;Takayuki Ogino ,&nbsp;Hironao Yasuoka ,&nbsp;Hideki Iijima ,&nbsp;Tsunekazu Mizushima","doi":"10.1016/j.prp.2024.155682","DOIUrl":"10.1016/j.prp.2024.155682","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), predominantly affects young patients and leads to intestinal complications. Amyloidosis, which involves abnormal protein deposition, is a serious complication of IBD, with a low incidence. Early detection of subclinical amyloid deposits is crucial for preventing fatal outcomes; however, routine investigations are lacking. We aimed to retrospectively examine subclinical amyloid deposition in adult patients with IBD. Surgical specimens from 249 patients with IBD were collected from the databases of two hospitals. The specimens were subjected to staining and immunohistochemistry, and clinical information was collected simultaneously. The amyloid positivity rate was 0.8 % in CD (1/131) and 0 % in UC (0/118) based on Congo red staining. The patient with amyloid deposits was a female in her 80 s who lacked a family history of amyloidosis. The subtype was amyloid A. Clinical history revealed intestinal resection in her 30 s and subsequent abdominal symptoms. To the best of our knowledge, this is the first study to collect &gt;100 surgically examined specimens from adults with CD or UC. In older patients with a long and complex clinical course, aggressive analysis of amyloids would be better.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155682"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonsense-mediated mRNA decay: Physiological significance, mechanistic insights and future implications","authors":"Asish Kumar Patro,&nbsp;Gagan Kumar Panigrahi,&nbsp;Sanjoy Majumder,&nbsp;Rutupurna Das,&nbsp;Annapurna Sahoo","doi":"10.1016/j.prp.2024.155677","DOIUrl":"10.1016/j.prp.2024.155677","url":null,"abstract":"<div><div>Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades premature aberrant transcripts and importantly, it also takes part in gene expression regulation by regulating the endogenous transcripts. NMD distinguishes aberrant and non-aberrant transcript by looking after the NMD signatures such as long 3′ UTR. NMD modulates cellular surveillance and eliminates the plausible synthesis of truncated proteins as because if the aberrant mRNA escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. NMD involves multiple proteins and any alteration or mutation within these proteins results in various pathophysiological consequences. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. In this review, we have shed light on the core and associated proteins of NMD, further summarized the mechanism of the NMD pathway and also described the implications of mutations in NMD factors resulting in severe pathological conditions including neurodevelopmental disorder, effects on male sterility and cancer. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases. This review summarizes the current understanding of NMD and its role in controlling various cellular processes in both development and disease.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155677"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNAs as the pivotal regulators of epithelial mesenchymal transition through WNT/β-catenin signaling pathway in tumor cells","authors":"Faezeh Tolue Ghasaban,&nbsp;Meysam Moghbeli","doi":"10.1016/j.prp.2024.155683","DOIUrl":"10.1016/j.prp.2024.155683","url":null,"abstract":"<div><div>Tumor cell invasion is considered as one of the main therapeutic challenges in cancer patients, which leads to distant metastasis and reduced prognosis. Therefore, investigation of the factors involved in tumor cell invasion improves the therapeutic methods to reduce tumor metastasis. Epithelial-mesenchymal transition (EMT) process has a pivotal role in tumor cell invasion and metastasis, during which tumor cells gain the invasive ability by losing epithelial characteristics and acquiring mesenchymal characteristics. WNT/β-catenin signaling pathway has a key role in tumor cell invasion by regulation of EMT process. Long non-coding RNAs (lncRNAs) have also an important role in EMT process through the regulation of WNT/β-catenin pathway. Deregulation of lncRNAs is associated with tumor metastasis in different tumor types. Therefore, in the present review, we investigated the role of lncRNAs in EMT process and tumor cell invasion through the regulation of WNT/β-catenin pathway. It has been reported that lncRNAs mainly induced the EMT process and tumor cell invasion through the activation of WNT/β-catenin pathway. LncRNAs that regulate the WNT/β-catenin mediated EMT process can be introduced as the prognostic markers as well as suitable therapeutic targets to reduce the tumor metastasis in cancer patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155683"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A complete sojourn on exosomes: Potential diagnostic and therapeutic agents","authors":"Sonakshi Garg ,&nbsp;Gurisha Garg ,&nbsp;Preeti Patel ,&nbsp;Manish Kumar ,&nbsp;Shubham Thakur ,&nbsp;Nitin Sharma ,&nbsp;Balak Das Kurmi","doi":"10.1016/j.prp.2024.155674","DOIUrl":"10.1016/j.prp.2024.155674","url":null,"abstract":"<div><div>Exosomes are vesicles produced by the human body for carrying certain information from one cell to another. The carriers are nanosized vesicles carrying a wide variety of cargo like RNA, DNA, and proteins. Exosomes are also being used in the early diagnosis of various diseases and disorders. Current research focuses on exosomes tailoring for achieving therapeutic potential in various diseases and disorders. Besides this, their biocompatibility, stability, adjustable efficacy, and targeting properties make them attractive vehicles for formulation developers. Various preclinical studies suggested that the exosome culture cells are also modified with certain genes to achieve the desirable properties of resultant exosomes. The human body also produces some other vesicles like Ectosomes and Exomeres produced along with exosomes. Additionally, vesicles like Migrasomes are produced by migrating cells and apoptotic bodies, and Oncosomes are produced by cancer cells which can also be useful for the diagnosis of various diseases and disorders. For the separation of desired exosomes from other vesicles some latest techniques that can be useful viz differential centrifugation, density gradient centrifugation, and immunoaffinity purification have been discussed. Briefly, this review summarized various techniques of isolation of purified exosomes along with an overview of the application of exosomes in various neurodegenerative disorders and cancer along with various latest aspects of exosomes in disease progression and management which might be beneficial for the researchers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155674"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSTM1 and GSTT1 deletions in penile cancer are associated with TNM stage but not with HPV DNA status","authors":"Ana Paula Abreu ,&nbsp;Jhessica Gomes ,&nbsp;Jucileide Mota ,&nbsp;Ana Paula Almeida ,&nbsp;Rita Carvalhal ,&nbsp;Flávia Vidal ,&nbsp;Rui Medeiros ,&nbsp;Hugo Sousa ,&nbsp;Melaine Lawall ,&nbsp;Rui M. Gil da Costa ,&nbsp;Haissa O. Brito ,&nbsp;Luciane M.O. Brito","doi":"10.1016/j.prp.2024.155686","DOIUrl":"10.1016/j.prp.2024.155686","url":null,"abstract":"<div><div>Deletions of the <em>GSTT1</em> and <em>GSTM1</em> are associated with chemical carcinogenesis and genitourinary malignancies like bladder cancer, where they correlate with increased tumor aggressiveness. In uterine cervical lesions, <em>GSTT1</em> and <em>GSTM1</em> deletions have also been suggested to facilitate the persistence of human papillomavirus (HPV) infection and HPV-induced carcinogenesis. This work addresses the hypothesis that <em>GSTT1</em>/<em>GSTM1</em> deletions are associated with presence of HPV DNA and aggressiveness in penile cancer, a rare malignancy with HPV+ and HPV- subtypes. Tumor DNA samples and medical records from HPV+ and HPV- penile cancer patients were analyzed. Each sample was screened for <em>GSTT1</em> and <em>GSTM1</em> deletions and for the presence of HPV DNA using PCR-based techniques. 74.5 % of samples contained HPV DNA. 61.8 % of cases showed T2 and T3 staging. There were no differences in the frequencies of <em>GSTT1/GSTM1</em> genotypes between HPV+ and HPV- cases (<em>p</em>&gt;0.05). <em>GSTT1</em>^wt/<em>GSTM</em>^{<em>null</em>} patients were more likely to have higher TNM stages compared with other genotypes (<em>p</em>=0.012), but no differences were observed concerning perineural invasion nor lymphovascular invasion. These findings indicate that <em>GSTT1</em> and <em>GSTM1</em> deletions are common in HPV+ and HPV- penile cancers. <em>GSTM1</em> deletions in the presence of wild-type <em>GSTT1</em> seems to be associated with tumor progression, and additional studies are warranted to confirm its potential as a prognostic marker in penile cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155686"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular responses to neoadjuvant FOLFOX6-bevacizumab treatment in colorectal cancers analyzed by single-cell transcriptome analysis","authors":"Sun Shin ,&nbsp;Hyun Ho Kim ,&nbsp;Jae Woong Kim ,&nbsp;Doeun Rim ,&nbsp;Changhyeok An ,&nbsp;Yeun-Jun Chung ,&nbsp;Sug Hyung Lee","doi":"10.1016/j.prp.2024.155681","DOIUrl":"10.1016/j.prp.2024.155681","url":null,"abstract":"<div><div>Neoadjuvant chemotherapy combined with bevacizumab is used to treat colorectal cancer (CRC) patients by targeting tumor and vascular cells. However, it is known that other cells in the tumor microenvironment (TME) also change in response to this treatment. To investigate the changes in TME subpopulations in response to neoadjuvant FOLFOX6 plus bevacizumab, we studied pre- and post-treatment CRC tissues in four patients using single-cell RNA sequencing (scRNA-seq). This analysis classified nine cell types, including epithelial, vascular, immune cells, and fibroblasts. The cellular responses were widespread across the cell types, but there were specific subpopulations that altered, especially in vascular, immune, and fibroblast cells. In vascular subpopulations, CDH13-endothelial, arteriole, and CA4 capillary cells were selectively reduced. In immune cells, CD4+, CD8+ T cells, conventional dendritic cell type 1 (cDC1), and <em>CCL19</em>-expressing migrating DC (migDC-1) increased, while Th17, Th22, and tumor-associated macrophage (TAM) cells decreased, indicating that the treatment might be immunostimulatory. In fibroblasts, two major cancer-associated fibroblasts (matrix CAF (mCAF) and inflammatory CAF (iCAF)) increased, while conventional fibroblasts decreased, suggesting that the treatment remodeled the reparative/inflammatory processes, which might lead to reduced aggressiveness from the cancer-associated fibroblasts. In summary, our study reveals that neoadjuvant FOLFOX6 plus bevacizumab leads to alterations in particular subpopulations of vascular, immune, and reparative/inflammatory cells in the TME of CRCs. These alterations include vascular reduction, immunologic stimulation, and reduction of cancer-associated fibroblasts, which may underlie the responsiveness to the therapy in CRC. Our results may provide insights into the mechanisms of responsiveness/resistance to neoadjuvant FOLFOX6 plus bevacizumab therapy in CRCs.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155681"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}