Translational cancer research最新文献

{"title":"The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways.","authors":"An Wang, Youbo Wang, Yanhui Chen, Posum Wan, Anwaar Saeed, Qinyun Ma, Xiaofeng Chen","doi":"10.21037/tcr-24-1657","DOIUrl":"https://doi.org/10.21037/tcr-24-1657","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell cancer (ESCC) is the most common type of esophageal cancer. This study aimed to elucidate the role of Saccharomyces cerevisiae-like 4 (<i>SEC14L4</i>) in ESCC.</p><p><strong>Methods: </strong>To elucidate the role of <i>SEC14L4</i> in ESCC, this study analyzed the clinical data, gene sequencing data, and other relevant data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of the National Center for Biotechnology Information. The methodology involved several analytical approaches, including nomogram model analysis, co-expression analysis, gene set enrichment and variation analysis, weighted correlation network analysis, drug susceptibility analysis, and single-cell analysis. These methods were employed to evaluate the significance of SEC14L4 in ESCC. The expression of <i>SEC14L4</i> was evaluated via quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong><i>SEC14L4</i> expression (P<0.001) was significantly elevated in those with ESCC, especially in patients with locally advanced disease (P=0.005), and indicated a poor prognosis (P=0.045). Findings from the nomogram model analysis identified the contribution of clinical indicators to survival prediction with good efficacy. Subsequently, the single-nucleotide polymorphisms and co-expressed genes of <i>SEC14L4</i> were identified. Furthermore, pathways associated with <i>SEC14L4</i>, including DNA metabolic process, transcription factor binding, apoptosis, and others, were examined. Notably, <i>SEC14L4</i> expression was predominantly observed in monocytes. Drug sensitivity analysis indicated the association of <i>SEC14L4</i> expression with sensitivity of ESCC to the common chemotherapy drugs AICAR, BMS.708163, GNF.2, Nutlin.3a, PD.0325901, and RDEA119. Verification of the high expression of <i>SEC14L4</i> in KYSE520 and KYSE150 was conducted, thereby confirming the study's findings.</p><p><strong>Conclusions: </strong>High expression of SEC14L4 is associated with poorer clinical outcomes, highlighting its potential as a therapeutic target and suggesting its involvement in the molecular mechanisms underlying ESCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5535-5549"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628780","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":"Krukenberg tumours: which patients should be considered for surgery?-a narrative literature review.","authors":"Sabina Ioana Nistor, Hooman Soleymani Majd","doi":"10.21037/tcr-24-904","DOIUrl":"https://doi.org/10.21037/tcr-24-904","url":null,"abstract":"<p><strong>Background and objective: </strong>Krukenberg tumours (KTs) are metastatic signet ring cell (SRC) adenocarcinomas of the ovary, arising from the stomach in most cases (70%). Other common primary sites are the colon, appendix and breast. The use of the term \"Krukenberg tumour\" is inconsistent in the literature which makes data interpretation difficult. Prognosis of KTs is dismal and, in the absence of randomised controlled trials, the best treatment strategies remain controversial. Evidence from retrospective studies suggests that metastectomy is associated with improved survival. Our narrative literature review set out to determine which patients gain maximal survival benefit from surgical management.</p><p><strong>Methods: </strong>A comprehensive literature search was performed using PubMed and Google Scholar databases, from 1 January 2000 to 15 July 2024, with the terms 'Krukenberg', 'metastatic mucinous adenocarcinoma of ovary'. This search identified 20 full-text manuscripts, including data on 1,815 patients.</p><p><strong>Key content and findings: </strong>We found that the overall prognosis of these patients remains poor, with a median overall survival (mOS) ranging between 9 and 50 months. Metastectomy is associated with survival benefit only when all visible disease is removed (R0): mOS in patients with microscopic residual disease (R1) or gross residual disease (R2) is similar to mOS in unresected patients (11 <i>vs.</i> 10 months). The following other factors have been identified as independent prognostic factors for survival in multivariate analyses: heated intraperitoneal chemotherapy (HIPEC), adjuvant chemotherapy, curative surgery for the primary tumour, i.e., gastrectomy, no ascites, non-gastric origin, a good performance status, less extensive metastatic disease, i.e., no extra-ovarian disease or no extra-pelvic disease, no peritoneal carcinomatosis or a low Peritoneal Cancer Index (PCI), smaller size of lesion, no SRC features, expression of oestrogen receptor-β (ER-β) and progesterone receptors (PR), metachronous tumours, linitis plastica, tumour grade.</p><p><strong>Conclusions: </strong>Multiple retrospective analyses have demonstrated that metastectomy is associated with a survival benefit in patients with metastatic mucinous ovarian adenocarcinomas. However, patients with poor prognostic factors are less likely to benefit from surgery and should be counselled accordingly. Diagnostic laparoscopy could be considered before debulking surgery, to assess resectability of disease and to avoid a futile exploratory laparotomy. HIPEC after cytoreductive surgery (CRS) remains controversial, with possible survival benefit for KTs of gastric origin, particularly when peritoneal dissemination is present but the PCI is low.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5664-5677"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628225","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":"ISL1 and AQP5 complement each other to enhance gastric cancer cell stemness by regulating CD44 expression.","authors":"Meng Jin, Guowei Zhang, Shouqi Wang, Rou Zhao, Haitao Zhang","doi":"10.21037/tcr-24-248","DOIUrl":"https://doi.org/10.21037/tcr-24-248","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer, a prevalent and life-threatening malignancy, is believed to involve cancer stem cells (CSCs) as a contributing factor to tumor progression. Insulin gene enhancer binding protein-1 (ISL1) is a transcription factor, and it has not been elucidated how ISL1 regulates gastric carcinogenesis. The aim of this paper is to investigate the role of ISL1 in gastric cancer development.</p><p><strong>Methods: </strong>In this study, we investigated the effects of ISL1 on the stem-like properties of human gastric cancer cells by applying transcriptional, flow, and immunofluorescence techniques.</p><p><strong>Results: </strong>In human gastric cancer samples, there is an observed elevation in ISL1 expression, which correlates with the expression of stem cell markers, notably LGR5. Functionally, ISL1 fosters the self-renewal, cell proliferation, migration, and the clonogenic potential of gastric cancer cells <i>in vitro</i>. Furthermore, it enhances the ability of these cells to form tumors and metastasize in vivo. Additionally, ISL1 collaborates with AQP5, collectively intensifying the tumorigenicity of gastric cancer cells. Mechanistically, transcriptomic analysis of cells overexpressing ISL1 unveils a notable activation of the forkhead box O (FOXO) pathway. This activation leads to increased nuclear expression of forkhead box O3 (FOXO3), subsequently resulting in elevated expression of the stemness-associated gene CD44 in gastric cancer cells.</p><p><strong>Conclusions: </strong>These findings shed light on the role of ISL1 in promoting the stem-like characteristics of gastric cancer cells and emphasize the connection between ISL1 and AQP5 as a novel therapeutic target for individuals with gastric cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5484-5496"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628086","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":"Optimal preservation condition for the extraction of cell-free DNA from bile of patients with biliary tract cancer.","authors":"Jian Yang, Teng Zhao, Baoning Nian, Chao Yang, Yu Zhu, Yongfu Xu, Xiaoya Xu, Sheng Chen, Zhikuan Li, Wei Zhang, Dadong Zhang, Kai Lu, Fabiao Zhang","doi":"10.21037/tcr-24-843","DOIUrl":"https://doi.org/10.21037/tcr-24-843","url":null,"abstract":"<p><strong>Background: </strong>Patients with biliary tract cancer (BTC) often have dismal outcomes due to the poor performance of traditional methods for early diagnosis. Recently, bile cell-free DNA (cfDNA) has been reported as a potential liquid biopsy material for BTC diagnosis. However, bile is a complex alkaline aqueous medium, and the proper storage conditions for bile remain to be explored. The aim of this study is to explore the effects of storing bile under various conditions on the stability of bile cfDNA and to determine the optimal conditions, thereby establishing a foundation for the subsequent application of bile cfDNA in liquid biopsy for early diagnostic and prognosis monitoring of patients with malignant BTC.</p><p><strong>Methods: </strong>We evaluated the storage temperature and storage time for the preservation of bile samples. Bile samples were collected in cfDNA tubes with protectant covered inside or regular tubes without, and the stability of bile cfDNA was analyzed during 10 days at room temperature (RT) or after 2 months of storage at low temperatures.</p><p><strong>Results: </strong>Bile cfDNA remained stable for bile samples being collected with cfDNA tubes and stored for 10 days at RT, while degraded with time for the case with regular tubes. When bile samples were collected with cfDNA tubes and stored for 2 months at 4 ℃, bile cfDNA remained stable, however, if collected with regular tubes, bile cfDNA exhibited a slight loss of integrity. No significant difference was observed for 2 months storage at -20 or -80 ℃.</p><p><strong>Conclusions: </strong>Our findings suggested that for bile cfDNA research, bile samples should be collected with cfDNA tubes and it can be transported for short-term shipment at RT, and could be stored at 4 ℃ with cfDNA tubes, or frozen at -20 ℃ with regular tubes.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5328-5338"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628686","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":"Exploring a specific type of tissue-resident natural killer cell involved in the anti-tumor and immunotherapy response in human papillomavirus-positive head and neck squamous cell carcinoma using scRNA-seq.","authors":"Wenrong Lin, Junwen Ding, Qian Li, Yuhao Lin, Shenjiong Ruan, Andrew C Birkeland, Jianming Ding","doi":"10.21037/tcr-24-1535","DOIUrl":"https://doi.org/10.21037/tcr-24-1535","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is an increasingly common malignancy. We aimed to explore the immune heterogeneity of natural killer (NK) cells in HPV-positive HNSCC.</p><p><strong>Methods: </strong>Single-cell RNA-sequencing (scRNA-seq) and bulk RNA-sequencing datasets of HPV-positive HNSCC data were obtained from the Gene Expression Omnibus (GEO) database. \"Seurat\", \"harmony\", and \"SingleR\" were used to perform the scRNA-seq analysis. Subsequently, the \"cellphonedb\" package was used for the cell crosstalk analysis, and the \"clusterProfiler\" package was used for the hallmark pathway enrichment analysis. Finally, the \"gene set variation analysis\" (\"GSVA\") package was used for the immune cell infiltration, Tumor Immune Dysfunction and Exclusion (TIDE), and risk-score analyses.</p><p><strong>Results: </strong>A total of 30,562 cells were classified into 9 cell clusters that comprised 6 main cell types [i.e., T cells, natural killer T (NKT) cells, NK cells, B cells, plasma cells, and macrophages]. The NK cells were then further clustered into 3 tissue-resident NK (trNK0-2) and 2 tumor-associated NK (taNK0-1) cell types. The trNK0 cell type, which exhibited inhibitory cancer hallmark activity, appeared to exert potential anti-tumor effects via trNK0-macrophage crosstalk. The trNK score could serve as an independent and valuable prognostic classifier, as the patients with high-trNK scores had better outcomes, immune-infiltration levels, and immunotherapy effects.</p><p><strong>Conclusions: </strong>Using an scRNA-seq analysis, we identified a specific type of tissue-resident NK cell (i.e., trNK-0) that was involved in the anti-tumor and immunotherapy response in HPV-positive HNSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5550-5562"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627480","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":"Integrated analysis reveals prognostic correlation and immune characteristics of a tumor-associated macrophage-based risk signature in triple-negative breast cancer.","authors":"Shichen Miao, Chengyu Bian, Jun Fang, Shanshan Wang, Huan You, Yi Zhou, Qichao Ni","doi":"10.21037/tcr-24-1037","DOIUrl":"https://doi.org/10.21037/tcr-24-1037","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages play a critical role in the progression and immune response of triple-negative breast cancer (TNBC). Our study aimed to explore the characteristics of tumor-associated macrophages (TAMs) in TNBC, construct a risk signature associated with TAM clusters, and verify its relationship with prognosis and immune-related characteristics.</p><p><strong>Methods: </strong>Firstly, we identified four TAM clusters and determined prognosis-related clusters in TNBC based on the single-cell RNA sequencing (scRNA-seq) data. Subsequently, the TAM-related prognostic genes were obtained by the univariate Cox regression analysis and an 8-gene risk signature was then constructed by least absolute shrinkage and selection operator (LASSO) regression based on these TAM-related prognostic genes. Analyses of immune characteristics showed a significant association between the signature with stromal and immune scores, as well as some immune cells.</p><p><strong>Results: </strong>Multivariate analysis revealed that the risk signature was an independent prognostic factor for TNBC, and its value in predicting immunotherapeutic outcomes was also confirmed. A novel nomogram integrating the stage and TAM-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of TNBC. Finally, the increasing expression of <i>GPR34</i> which is one of the eight hub genes was explored in TNBC by experiments including reverse-transcriptase polymerase chain reaction, western blot, and immunohistochemistry.</p><p><strong>Conclusions: </strong>Our study may provide unique insights into obtaining independent prognostic factors, improving immunotherapeutic strategies, and identifying effective therapeutic targets for TNBC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5214-5232"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628138","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":"Exploring SSR1 as a novel diagnostic and prognostic biomarker in hepatocellular carcinoma, and its relationship with immune infiltration.","authors":"Qingyu Xiao, Weixiang Qu, Wenying Shen, Zhen Cheng, Haijun Wu","doi":"10.21037/tcr-24-277","DOIUrl":"https://doi.org/10.21037/tcr-24-277","url":null,"abstract":"<p><strong>Background: </strong>Although signal sequence receptor subunit 1 (SSR1) has undergone thorough examination in different cancer types, its importance in hepatocellular carcinoma (HCC) remains largely uncharted and warrants further investigation. The aim of this study is to explore the role of SSR1 in HCC progression and to decipher its underlying molecular mechanisms.</p><p><strong>Methods: </strong>We employed the ONCOMINE, Tumor IMmune Estimation Resource (TIMER), and The Cancer Genome Atlas databases to assess SSR1 expression levels within tumor tissues. Logistic and Cox regression analyses, Kaplan-Meier survival plots, nomograms, and forest plots were employed to establish correlation between SSR1 and prognosis. Receiver operating characteristic (ROC) curves demonstrated diagnostic utility of SSR1. Additionally, Gene Ontology (GO) and gene set enrichment analysis (GSEA) analyses were conducted to uncover relevant molecular pathways. TIMER was instrumental in elucidating the connection between SSR1 and immune cell infiltration. Actions of SSR1 in HCC proliferation and migration were investigated through quantitative real-time polymerase chain reaction, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine cell proliferation assays, and Transwell migration and wound healing experiments.</p><p><strong>Results: </strong>Elevated SSR1 levels were found to be correlated with clinical parameters such as age and pathologic stage, thereby predicting a reduced overall survival (OS) rate in HCC patients. Multivariate survival analysis underscored SSR1 as an independent prognostic marker for OS. A nomogram underscored SSR1's effectiveness as a predictive tool for HCC outcomes, while ROC analysis indicated its high diagnostic accuracy. GO and GSEA analyses suggested that elevated SSR1 expression may be associated with epithelial-mesenchymal transition (EMT) pathway. SSR1 exhibited a negative correlation with cytotoxic cells and a positive correlation with Th2 cells. Our <i>in vitro</i> experiments provided evidence that heightened SSR1 levels may impact HCC proliferation and migration through EMT pathway.</p><p><strong>Conclusions: </strong>SSR1 surfaces as a new diagnostic and potentially prognostic biomarker, showing an association with immune cell infiltration and cell proliferation in HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5278-5299"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627882","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":"Construction and validation of prognostic model for colorectal mucinous adenocarcinoma patients and identification of a new prognosis related gene <i>FAM174B</i>.","authors":"Xiangwen Tan, Qing Fang, Yunhua Xu, Shuxiang Li, Jinyi Yuan, Kunming Xu, Xiguang Chen, Guang Fu, Yarui Liu, Qiulin Huang, Xiuda Peng, Shuai Xiao","doi":"10.21037/tcr-24-347","DOIUrl":"https://doi.org/10.21037/tcr-24-347","url":null,"abstract":"<p><strong>Background: </strong>Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of colorectal cancer (CRC) with distinct medical, disease-related, and genetic characteristics. The prognosis of MAC is generally poorer less favorable compared to non-specific adenocarcinoma (AC), but the prognostic indicator of MAC is rare. Therefore, this study aims to identify potential biomarkers and construct a prognostic model to better predict patient outcomes in MAC.</p><p><strong>Methods: </strong>We conducted differential genes expression investigation, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to pinpoint hub genes. Then, the hub genes were used to construct a prognostic model for MAC. Kaplan-Meier survival, receiver operating characteristic (ROC), and Cox regression analysis were used to assess the prognostic utility of the model. The potential biological function of the hub gene was examined using gene set enrichment analysis (GSEA).</p><p><strong>Results: </strong>Four hub genes, <i>FAM174B</i>, <i>CREB3L1</i>, <i>SPDEF</i>, and <i>RAP1GAP</i>, were identified between MAC and AC by differential genes expression analysis, WGCNA, and LASSO regression analysis. The prognostic signature model was constructed based on these four hub genes, which could divide MAC into low- and high-risk groups. The overall survival (OS) was notably lower in the high-risk group compared to the low-risk group (P=0.007). The area under the curves (AUCs) for 1-, 3-, and 5-year OS were 0.61 [95% confidence interval (CI): 0.73-0.49], 0.69 (95% CI: 0.76-0.63), and 0.77 (95% CI: 0.83-0.71), respectively. We also found that <i>FAM174B</i> expression was closely related to the OS of MAC (P=0.02). Further, the expression of <i>FAM174B</i> was positively correlated with MAC's Mucin type O-glycan biosynthesis. Finally, it was indicated that <i>FAM174B</i> was positively correlated with the critical molecules of mucus formation, <i>MUC5AC</i> (P=0.004, r=0.33), <i>MUC5B</i> (P<0.001, r=0.43), and <i>MUC2</i> (P<0.001, r=0.39).</p><p><strong>Conclusions: </strong>We have developed and validated a four-gene prognostic model to predict the survival of MAC. Additionally, we found that <i>FAM174B</i> might correlate with mucin production in MAC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5233-5246"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626539","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":"Exosomal AHSG in ovarian cancer ascites inhibits malignant progression of ovarian cancer by p53/FAK/Src signaling.","authors":"Guangyan Xie, Yongli Zhang, Jiachen Ma, Xiaoli Guo, Jiahao Xu, Linna Chen, Jingbo Zhang, Yanyu Li, Bei Zhang, Xueyan Zhou","doi":"10.21037/tcr-24-789","DOIUrl":"https://doi.org/10.21037/tcr-24-789","url":null,"abstract":"<p><strong>Background: </strong>The primary cause of mortality in patients with ovarian cancer (OC) is tumor metastasis. A comprehensive understanding of the mechanisms underlying metastasis in OC is essential for accurate prognosis prediction and the development of targeted therapeutic agents. Our findings indicate that alpha-2 Heremans Schmid glycoprotein (AHSG) is downregulated in OC exosomes. Consequently, the objective of this study was to identify novel prognostic markers and potential therapeutic targets for OC.</p><p><strong>Methods: </strong>Exosomes derived from OC cells and patient ascites were purified and applied to OC cells to assess their migratory ability using wound-healing and transwell assays. AHSG expression was enhanced by overexpressing lentivirus, and the resulting exosomes were isolated and co-cultured with OC cells to verify their effect on the migration ability of OC.</p><p><strong>Results: </strong>Exosomes in ovarian malignant ascites have been demonstrated to promote OC metastasis. However, our findings indicate that AHSG is down-regulated in OC tissues and ascites exosomes. Furthermore, overexpression of AHSG in OC cells has been shown to markedly decrease their migratory ability, as well as reduce the migratory ability of cancer cells after co-culture of its exosomes with cancer cells.</p><p><strong>Conclusions: </strong>The low expression of AHSG in exosomes derived from OC tissues and ascites is associated with metastatic progression in OC patients. Additionally, cancer-derived AHSG can be transported to OC cells via exosomes, where it inhibits OC migration <i>in vitro</i> and <i>in vivo</i> by regulating the p53/FAK/Src signaling pathway. The present study demonstrated that AHSG, derived from cancer cells, exerts a negative regulatory effect on OC cell motility, migration, and metastasis. These findings suggest that AHSG is a potential candidate for OC treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5365-5380"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627325","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":"Establishment and validation of a prediction model for gastric cancer with perineural invasion based on preoperative inflammatory markers.","authors":"Pan Jiang, Lijun Zheng, Yining Yang, Dongping Mo","doi":"10.21037/tcr-24-481","DOIUrl":"https://doi.org/10.21037/tcr-24-481","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a prevalent malignant tumor of the digestive system, characterized by a poor prognosis and high recurrence rate. Perineural invasion (PNI), the neoplastic infiltration of nerves, is a significant predictor of survival outcome in GC. Accurate preoperative identification of PNI could facilitate patient stratification and optimal preoperative treatment. We therefore established and validated a preoperative risk assessment model for GC patients with PNI.</p><p><strong>Methods: </strong>We collected data from 1,195 patients who underwent surgical resection at our hospital between October 2020 and December 2023, with PNI confirmed by pathological examination. We gathered laboratory data, including blood cell count, blood type, coagulation index, biochemical indexes, and tumor markers. Eligible patients were randomly divided into a training set and a testing set at a ratio of 7:3. The important risk factors of PNI were evaluated by random forest package in RStudio. Receiver operating characteristic-area under the curve (ROC-AUC) analysis was used to evaluate the discriminatory ability of the factors for PNI. Univariate and multivariate logistic regression analyses were utilized to verity independent risk factors for patients with PNI, and the logistic regression model and nomogram were constructed based on the results. Calibration curve and decision curve analysis (DCA) were conducted to assess the predictive model. Finally, we verified the prediction equation model using the testing set.</p><p><strong>Results: </strong>In the training set, 416 GC patients were pathologically diagnosed with PNI. The top 5 important risk factors for PNI were identified as carcinoembryonic antigen (CEA), fibrinogen-to-lymphocyte ratio (FLR), D-dimer, platelet-to-lymphocyte ratio (PLR), and carbohydrate antigen 19-9 (CA19-9), with optimal cut-off values of 3.89 ng/mL, 2.08, 0.24 mg/L, 122.37, and 14.85 U/mL, respectively. Multivariate logistic regression analysis confirmed that CEA, FLR, D-dimer, PLR, CA19-9, and CA72-4 as independent risk factors for PNI (P<0.05). We formulated the following predictive equation: Logit(P) = -1.211 + 0.695 × CEA + 0.546 × FLR + 0.686 × D-dimer + 0.653 × PLR + 0.515 × CA19-9 + 0.518 × CA72-4 (χ²=105.675, P<0.001). The model demonstrated an ROC-AUC value of 0.719 [95% confidence interval (CI): 0.681-0.757] in the training set, with a sensitivity of 68.51% and a specificity of 67.60%. The ROC-AUC value was 0.791 (95% CI: 0.750-0.831) in the testing set (sensitivity: 69.57%, specificity: 56.41%). Calibration curve and DCA confirmed that the model has good discrimination and accuracy.</p><p><strong>Conclusions: </strong>We successfully established and validated a prediction model for GC patients with PNI based on hematological indicators, hoping that this model can provide an adjunctive tool for predicting PNI in clinical work.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5381-5394"},"PeriodicalIF":1.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626825","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}