Cancer Biomarkers最新文献

{"title":"KIAA1429-mediated RXFP1 attenuates non-small cell lung cancer tumorigenesis via N6-methyladenosine modification.","authors":"Zhixiang Zhang, Jipeng Guo, Chongwen Gong, Sai Wu, Yanlei Sun","doi":"10.3233/CBM-230188","DOIUrl":"https://doi.org/10.3233/CBM-230188","url":null,"abstract":"<p><strong>Background: </strong>N6-methyladenosine (m6A) modification has been associated with non-small cell lung cancer (NSCLC) tumorigenesis.</p><p><strong>Objectives: </strong>This study aimed to determine the functions of Vir-like m6A methyltransferase-associated (KIAA1429) and relaxin family peptide receptor 1 (RXFP1) in NSCLC.</p><p><strong>Methods: </strong>A quantitative real-time polymerase chain reaction was used to analyze the mRNA levels of KIAA1429 and RXFP1 in NSCLC. After silencing KIAA1429 or RXFP1 in NSCLC cells, changes in the malignant phenotypes of NSCLC cells were assessed using cell counting kit-8, colony formation, and transwell assays. Finally, the m6A modification of RXFP1 mediated by KIAA1429 was confirmed using luciferase, methylated RNA immunoprecipitation, and western blot assays.</p><p><strong>Results: </strong>KIAA1429 and RXFP1 were upregulated and downregulated in NSCLC, respectively. Silencing of KIAA1429 attenuated the viability, migration, and invasion of NSCLC cells, whereas silencing of RXFP1 showed the opposite function in NSCLC cells. Moreover, RXFP1 expression was inhibited by KIAA1429 via m6A-modification. Therefore, silencing RXFP1 reversed the inhibitory effect of KIAA1429 knockdown in NSCLC cells.</p><p><strong>Conclusion: </strong>Our findings confirmed that the KIAA1429/RXFP1 axis promotes NSCLC tumorigenesis. This is the first study to reveal the inhibitory function of RXFP1 in NSCLC via KIAA1429-mediated m6A-modification. These findings may help identify new biomarkers for targeted NSCLC therapy.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013816","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":"Radiomics and artificial intelligence for risk stratification of pulmonary nodules: Ready for primetime?","authors":"Roger Y Kim","doi":"10.3233/CBM-230360","DOIUrl":"10.3233/CBM-230360","url":null,"abstract":"<p><p>Pulmonary nodules are ubiquitously found on computed tomography (CT) imaging either incidentally or via lung cancer screening and require careful diagnostic evaluation and management to both diagnose malignancy when present and avoid unnecessary biopsy of benign lesions. To engage in this complex decision-making, clinicians must first risk stratify pulmonary nodules to determine what the best course of action should be. Recent developments in imaging technology, computer processing power, and artificial intelligence algorithms have yielded radiomics-based computer-aided diagnosis tools that use CT imaging data including features invisible to the naked human eye to predict pulmonary nodule malignancy risk and are designed to be used as a supplement to routine clinical risk assessment. These tools vary widely in their algorithm construction, internal and external validation populations, intended-use populations, and commercial availability. While several clinical validation studies have been published, robust clinical utility and clinical effectiveness data are not yet currently available. However, there is reason for optimism as ongoing and future studies aim to target this knowledge gap, in the hopes of improving the diagnostic process for patients with pulmonary nodules.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013817","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":"Uncovering the link between human endogenous retroviruses, inflammatory pathways, and gastric cancer development.","authors":"Zhengtai Li, Hongjiang Li, Kun Fang, Xinglei Lin, Changyuan Yu","doi":"10.3233/CBM-230417","DOIUrl":"10.3233/CBM-230417","url":null,"abstract":"<p><strong>Background: </strong>Endogenous retroviruses, previously deemed \"junk\" DNA, have gained attention in recent scientific studies. These inherited genomic elements are now recognized for their potential roles in diseases, especially cancer, highlighting their value as potential diagnostic or therapeutic targets.</p><p><strong>Objective: </strong>This research aims to explore the association between human endogenous retroviruses (HERV) and gastric cancer, focusing on discerning HERV expression patterns and understanding their implications in gastric cancer pathology.</p><p><strong>Methods: </strong>A quantitative analysis of HERV expression was conducted, employing Support Vector Machine (SVM) and AdaBoost algorithms to identify discriminative HERVs. The co-regulation network between protein-coding genes and HERVs was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA).</p><p><strong>Results: </strong>Three distinct HERVs (LTR16A|72|451, LTR91|636|874, LTR27D|87|222) were identified as significantly different. Strong correlations were found between HERVs, and gene sets enriched in the inflammatory pathway.</p><p><strong>Conclusions: </strong>HERVs appear to influence abnormal inflammatory responses, suggesting a pivotal role in gastric cancer development.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333437","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":"A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer.","authors":"Zhi Yi Zhao, Yin Cao, Hong Liang Wang, Ling Yun Liu","doi":"10.3233/CBM-230216","DOIUrl":"10.3233/CBM-230216","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC.</p><p><strong>Methods: </strong>We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507.</p><p><strong>Results: </strong>Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1-penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group's OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score.</p><p><strong>Conclusions: </strong>The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673684","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":"The prognostic and antitumor roles of key genes of ferroptosis in liver hepatocellular cancer and stomach adenocarcinoma.","authors":"Wenceng Pei, Minren Jiang, Haiyan Liu, Jiahong Song, Jian Hu","doi":"10.3233/CBM-230114","DOIUrl":"10.3233/CBM-230114","url":null,"abstract":"<p><strong>Background: </strong>Liver hepatocellular cancer (LIHC) and stomach adenocarcinoma (STAD) are common malignancies with high lethal ratios worldwide. Great progress has been achieved by using diverse therapeutic strategies; however, these diseases still have an unfavourable prognosis. Ferroptosis inducer drugs, unlike apoptosis-related drugs, can overcome the resistance to cancer therapy caused by traditional chemicals. However, the relationship between overall survival (OS) and ferroptosis-related genes, as well as the mechanisms involved, are largely unclear.</p><p><strong>Methods: </strong>The expression levels of AIFM2, GPX4, ACSL4, FTH1, NOS1, and PTGS2 in LIHC and STAD were obtained from UALCAN. The correlations of OS with these gene expression levels were obtained using the Kaplan-Meier Plotter database. The OS associated with genetic mutations of those genes compared to that of unchanged genes was analysed using the TIMER website. GO and KEGG enrichment analyses of ferroptosis-related genes and their coexpressed genes in LIHC and STAD were conducted using the STRING and DAVID databases. The relationship of PTGS2 and ACSL4 to immune cell infiltration was analysed using the TIMER website. The viability and GPX5 expression levels in LIHC cells treated with RSL3 and As2O3 were detected by MTT methods and western blotting, respectively.</p><p><strong>Results: </strong>Our results showed that GPX4, FTH1 and AIFM2 were overexpressed in LIHC and STAD. High levels of GPX4, FTH1 and AIFM2 were prominently correlated with better prognosis in LIHC. However, GPX and FTH1 in STAD did not show significant correlations with OS. AIFM2 in STAD had the opposite trend with OS compared with that in LIHC. Moreover, a high mutation rate of these genes (35.74%) was also observed in LIHC patients, and genetic mutation of these genes was correlated with shorter OS. In contrast, the genetic mutation of these genes did not change OS in STAD. Enrichment analysis showed that the respiratory electron transport chain, cell chemotaxis and T-cell migration were related to ferroptosis. ASCL4 and PTGS2 coexpressed with cytokines associated with immune cell infiltration. Compared to RSL3 or As2O3 alone, As2O3 plus RSL3 significantly inhibited the growth of Huh7 cells. GPX4 was downregulated to an undetectable level when in combination with RSL3.</p><p><strong>Conclusions: </strong>Our results indicated that ferroptosis-related genes might play an important role in LIHC and STAD and might be risk factors for overall survival in LIHC and STAD.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941349","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":"Long non-coding RNAs PTENP1, GNG12-AS1, MAGI2-AS3 and MEG3 as tumor suppressors in breast cancer and their associations with clinicopathological parameters.","authors":"Luděk Záveský, Eva Jandáková, Vít Weinberger, Luboš Minář, Milada Kohoutová, Ondřej Slanař","doi":"10.3233/CBM-230259","DOIUrl":"10.3233/CBM-230259","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease.</p><p><strong>Objective: </strong>Evaluation of novel long non-coding RNAs biomarkers for breast cancer.</p><p><strong>Methods: </strong>The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics.</p><p><strong>Results: </strong>The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality.</p><p><strong>Conclusions: </strong>The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567654","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":"Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.","authors":"Gehan Hammad, Samah Mamdouh, Dina Mohamed Seoudi, Mohamed Ismail Seleem, Gehan Safwat, Rania Hassan Mohamed","doi":"10.3233/CBM-230134","DOIUrl":"10.3233/CBM-230134","url":null,"abstract":"<p><strong>Background: </strong>P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features.</p><p><strong>Methods: </strong>The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis.</p><p><strong>Results: </strong>Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant.</p><p><strong>Conclusion: </strong>PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479472","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":"Identification of Hub genes with prognostic values in colorectal cancer by integrated bioinformatics analysis.","authors":"Shan Li, Ting Li, Yan-Qing Shi, Bin-Jie Xu, Yu-Yong Deng, Xu-Guang Sun","doi":"10.3233/CBM-230113","DOIUrl":"10.3233/CBM-230113","url":null,"abstract":"<p><strong>Background: </strong>Our study aimed to investigate the Hub genes and their prognostic value in colorectal cancer (CRC) via bioinformatics analysis.</p><p><strong>Methods: </strong>The data set of colorectal cancer was downloaded from the GEO database (GSE21510, GSE110224 and GSE74602) for differential expression analysis using the GEO2R tool. Hub genes were screened by protein-protein interaction (PPI) comprehensive analysis. GEPIA was used to verify the expression of Hub genes and evaluate its prognostic value. The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database. The cBioPortal was used to analyze the type and frequency of Hub gene mutations, and the effects of mutation on the patients' prognosis. The TIMER database was used to study the correlation between Hub genes and immune infiltration in CRC. Gene set enrichment analysis (GSEA) was used to explore the biological function and signal pathway of the Hub genes and corresponding co-expressed genes.</p><p><strong>Results: </strong>We identified 346 differentially expressed genes (DEGs), including 117 upregulated and 229 downregulated. Four Hub genes (AURKA, CCNB1, EXO1 and CCNA2) were selected by survival analysis and differential expression validation. The protein and mRNA expression levels of AURKA, CCNB1, EXO1 and CCNA2 were higher in CRC tissues than in adjacent tissues. There were varying degrees of immune cell infiltration and gene mutation of Hub genes, especially B cells and CD8+ T cells. The results of GSEA showed that Hub genes and their co-expressed genes mainly participated in chromosome segregation, DNA replication, translational elongation and cell cycle.</p><p><strong>Conclusion: </strong>Overexpression of AURKA, CCNB1, CCNA2 and EXO1 had a better prognosis for CRC and this effect was correlation with gene mutation and infiltration of immune cells.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941350","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":"Differentially expressed microRNA in prognosis of gastric cancer with Lauren classification.","authors":"Wenjiao Chen, Qin Guo, Huo Zhang, Yiping Du, Yan Zhou, Zebo Huang, Meiling Zhang, Songbing Qin","doi":"10.3233/CBM-230303","DOIUrl":"10.3233/CBM-230303","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification.</p><p><strong>Methods: </strong>A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification.</p><p><strong>Results: </strong>Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p.</p><p><strong>Conclusions: </strong>Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037848","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":"RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients.","authors":"María Belén Giorello, Francisco Raúl Borzone, María Florencia Mora, María Del Rosario Padin, Alejandra Wernicke, Vivian Labovsky, Norma Alejandra Chasseing","doi":"10.3233/CBM-230523","DOIUrl":"10.3233/CBM-230523","url":null,"abstract":"<p><strong>Background: </strong>The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment.</p><p><strong>Methods and results: </strong>We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p= 0.006), shorter metastasis-free survival (MFS) [p= 0.007, OR (95%CI) = 2.290 (1.259-4.156)], and lower overall survival (OS) [p= 0.004, OR (95%CI) = 2.469 (1.343-4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs.</p><p><strong>Conclusions: </strong>These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141869","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}