Cancer Genomics & Proteomics最新文献

{"title":"Integrated Proteomics Reveal ALDH1A1 as an Oncogenic Driver and Regulatory Hub in Hepatocellular Carcinoma.","authors":"Hanxun Yue, Zenan Hu, Guozhi Wu, Renpeng Li, N A Jiang, Y A Zheng, Yuping Wang, Yongning Zhou","doi":"10.21873/cgp.20582","DOIUrl":"10.21873/cgp.20582","url":null,"abstract":"<p><strong>Background/aim: </strong>Although aldehyde dehydrogenases 1 family member A1 (ALDH1A1) has been extensively studied in cancer, its role in hepatocellular carcinoma (HCC) remains poorly understood. This study was designed to characterize the expression pattern and functional roles of ALDH1A1 in HCC, and to further investigate its underlying molecular mechanisms using integrated proteomic analysis.</p><p><strong>Materials and methods: </strong>This study performed a pan-cancer analysis of ALDH1A1 expression, followed by validation of its expression levels in HCC tissue samples and cell lines. The expression of ALDH1A1 was manipulated using small interfering RNAs and lentiviral vector in HCC cell lines. And then the proliferation, migration, invasion, and tumorigenicity of HCC cells were observed <i>in vitro</i> and <i>in vivo</i>. Quantitative proteomic and phosphoproteomic profiling were conducted by liquid chromatography-tandem mass spectrometry, with comprehensive analyses and key findings validated by experiments.</p><p><strong>Results: </strong>ALDH1A1 was highly expressed in HCC tissues but exhibited notable expression heterogeneity among HCC cell lines. Functionally, ALDH1A1 promoted the proliferation, migration, and tumorigenicity of HCC cells, while suppressing apoptosis and modestly attenuates invasion. Quantitative proteomic and phosphoproteomic analyses revealed that ALDH1A1 profoundly reshaped both protein expression and phosphorylation landscapes in HCC. Furthermore, we validated that ALDH1A1 positively regulates the expression of DMPK, PCMTD2, VAMP4, ARHGAP19, NOL4L, and ST7, while suppressing SLC31A1, DSTYK, CYP4F12, GPNMB expression. Rescue experiments indicated that ALDH1A1 may promote HCC <i>via</i> activating Rho family small GTPase. ALDH1A1 also significantly upregulated mTOR phosphorylation.</p><p><strong>Conclusion: </strong>ALDH1A1 acts as an oncogenic driver and regulatory hub in HCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"407-429"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763204","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":"Cancer Cytogenetics: Deep Roots, New Branches in the Age of Omics.","authors":"Ioannis Panagopoulos","doi":"10.21873/cgp.20580","DOIUrl":"10.21873/cgp.20580","url":null,"abstract":"<p><p>For decades, the \"death of cancer cytogenetics\" has been repeatedly proclaimed and has grown louder in the era of omics. However, cytogenetics continues to evolve, retaining its central role in the study of chromosomes. From the microscopic visualization of numerical and structural aberrations using staining and banding techniques, the field has steadily incorporated new methodologies, including fluorescence <i>in situ</i> hybridization, array comparative genomic hybridization, high-throughput sequencing, and, most recently, optical genome mapping. These approaches have revealed unprecedented details of chromosome structure and behavior, uncovered catastrophic genomic events in cancer, and given rise to new concepts such as cytogenomics and chromosomics. Although cytogenetics is sometimes viewed as synonymous with chromosome banding, its scope, namely the study of chromosome structure and behavior, extends far beyond any single method. Chromosomes remain indispensable for understanding genome architecture, chromosomal instability, and fusion-gene mechanisms in neoplasia, irrespective of the technologies applied. Rooted in its past yet continually branching outwards with each scientific advance, today's cytogenetics integrates classical and modern approaches, carrying forward the legacy of chromosome banding while adopting genome-wide technologies. These developments underscore the enduring importance of cytogenetics for interpreting the structural complexity of cancer genomes. This review aims to demonstrate that cytogenetics, far from being obsolete, remains a vital component of modern cancer research by highlighting essential insights into chromosome structure, genome architecture, and fusion-gene mechanisms in the era of -<i>omics</i>.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"342-392"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763192","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":"Effects of Isthmus Topography on the Molecular Characteristics of <i>BRAF</i>-mutant Papillary Thyroid Cancer.","authors":"Chi-Yu Kuo, Sheena Yi-Hsin Cheng, Yi-Chiung Hsu, Shih-Ping Cheng","doi":"10.21873/cgp.20585","DOIUrl":"10.21873/cgp.20585","url":null,"abstract":"<p><strong>Background/aim: </strong>Previous studies suggest that thyroid cancers in the isthmus are associated with more aggressive behavior and unfavorable patient outcomes compared to lobar tumors. This study aimed to characterize the molecular features of isthmus thyroid cancer.</p><p><strong>Materials and methods: </strong>Transcriptomic and proteomic data were retrieved from the Cancer Genome Atlas. We performed 1:2 propensity score matching based on age, sex, tumor subtype, size, extrathyroidal extension, lymph node metastasis, and stage, matching 15 papillary thyroid cancers with the <i>BRAF</i> V600E mutation located in the isthmus to 30 tumors in the unilateral lobar area.</p><p><strong>Results: </strong>Despite balanced oncogenic drivers, <i>BRAF</i>-mutant isthmus tumors exhibited significantly lower BRAF-RAS scores and higher ERK output scores. Additionally, these tumors had a slightly elevated DNA methylation-based stemness index. Principal component analysis revealed distinct gene expression patterns between the two groups. Differential expression and gene set enrichment analysis indicated enrichment in extracellular matrix remodeling, cell adhesion pathways, and TGF-β signaling. Notable upregulated genes included oligoadenylate synthases, <i>TNR, HAS3</i>, and <i>LIF</i>. Hierarchical proteomic clustering highlighted increased co-expression of several oncoproteins and DNA damage response markers in isthmus tumors.</p><p><strong>Conclusion: </strong><i>BRAF</i>-mutant papillary thyroid cancers in the isthmus display distinct molecular characteristics, including increased ERK signaling activity. These findings suggest that topographical location independently influences tumor biology and may account for the more aggressive clinical behavior of isthmus tumors at the molecular level.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"470-482"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763248","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":"Macrophage-related Genomic Signatures Predict HCC Prognosis and Therapy Response.","authors":"Wentao Zhong, Linqiang Duan, Feng Zhang, Changgui Zou, Junyi Qiu, Shixiong Hu, Min Yu, Z I Yin","doi":"10.21873/cgp.20587","DOIUrl":"10.21873/cgp.20587","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis due to drug resistance and recurrence. Tumor-associated macrophages (TAMs) are pivotal in the HCC tumor microenvironment, but their prognostic and therapeutic relevance remains incompletely defined. This study aimed to identify macrophage-related genomic signatures, delineate HCC molecular subtypes, and construct a prognostic model to predict survival and therapy response.</p><p><strong>Materials and methods: </strong>We integrated scRNA-seq (GSE151530) and bulk RNA-seq (HCCDB18, TCGA-HCC) data. Macrophage-related genes were identified via differential expression analysis of scRNA-seq data. Consensus clustering (Euclidean distance, hierarchical clustering) was used for subtype delineation. A prognostic model was constructed using PCA (Principal Component Analysis) on 25 OS-related differentially expressed genes (DEGs; univariate Cox regression), with z-scored normalization and 3 principal components. Immune infiltration (ssGSEA) and drug sensitivity [immunophenoscore (IPS) scores, pRRophetic] were analyzed.</p><p><strong>Results: </strong>Four HCC subtypes were identified; Cluster C showed the most favorable survival. The PCA-derived score strongly correlated with OS (<i>p</i><0.001) and immunotherapy responsiveness (higher scores=enhanced sensitivity). High scores were associated with increased effector T cell infiltration and reduced T cell exhaustion. Drug sensitivity analyses revealed divergent responses to immunotherapy and conventional agents across subgroups.</p><p><strong>Conclusion: </strong>Macrophage-related genomic signatures are critical for HCC prognosis and therapy response. The PCA-based model holds promise as a biomarker for personalized therapy, warranting larger cohort validation and mechanistic exploration.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"503-529"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763170","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":"Transcriptome-based Deep Learning Model for Predicting Gemcitabine and Cisplatin Chemotherapy Response in Urothelial Carcinoma: Development and External Validation.","authors":"Juwon Kang, Hyun Jung Lee, Sang-Bo Oh, Jong Kil Nam, Tae Un Kim, Hwaseong Ryu, Yong Kan Ki, Jihoon Kang, Yi Rang Kim, Jeong Hoon Lee, Junjeong Choi, Yun Jeong Hong, Kwonoh Park","doi":"10.21873/cgp.20589","DOIUrl":"10.21873/cgp.20589","url":null,"abstract":"<p><strong>Background/aim: </strong>Chemotherapy with gemcitabine and cisplatin remains the cornerstone of treatment for advanced urothelial carcinoma (UC), yet response rates vary significantly among patients. Predicting treatment response is crucial to avoid unnecessary toxicity and optimize therapeutic strategies. This study aims to develop a deep learning model leveraging RNA sequencing data to predict chemotherapy response in UC patients.</p><p><strong>Materials and methods: </strong>We developed a deep learning model using RNA sequencing gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus to predict chemotherapy (gemcitabine and cisplatin) response in UC patients. The model was externally validated using an independent cohort from the Pusan National University Yangsan Hospital. Model interpretation was performed through gene ontology and survival analyses using predictions from TCGA samples not included in the training set.</p><p><strong>Results: </strong>The deep learning model demonstrated excellent predictive performance, achieving 94.7% accuracy in the training dataset and 90.0% accuracy in external validation. Gene ontology analysis revealed four key functional clusters associated with chemotherapy response: DNA damage response, cell cycle regulation, kinesins/microtubule dynamics, and mitotic cytokinesis. Notably, the model showed significant prognostic value in early-stage, with predicted responders displaying markedly better survival outcomes (<i>p</i>=0.019).</p><p><strong>Conclusion: </strong>Our transcriptome-based deep learning approach offers a promising computational strategy for predicting chemotherapy response in urothelial carcinoma. By integrating high-dimensional RNA-seq data and advanced machine learning techniques, we provide a potential decision-support tool for personalized treatment planning.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"546-557"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763280","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":"Proximity Mapping of the ER Proteome Reveals Metastasis-specific Candidate Biomarkers in Breast Cancer Cell Lines.","authors":"Mehmet Sarihan, Elifcan Kocyigit, Murat Kasap, Gurler Akpinar","doi":"10.21873/cgp.20586","DOIUrl":"10.21873/cgp.20586","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancer is the most frequently diagnosed cancer among women. While biomarkers are critical for early detection and therapy, current markers lack sufficient specificity and sensitivity. The endoplasmic reticulum (ER) plays a central role in protein folding, post-translational modification, and lipid metabolism, and its alterations are linked to tumor progression. This study aimed to map ER proteome changes associated with breast cancer invasiveness and identify novel candidate biomarkers.</p><p><strong>Materials and methods: </strong>We compared the ER proteomes of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cell lines using an ER-targeted TurboID proximity labelling approach, followed by LC-MS/MS analysis. Bioinformatic analyses were performed to determine functional associations and differential expression related to invasion and metastasis for the candidate biomarkers.</p><p><strong>Results: </strong>A total of 2,079 proteins were identified, including 1,378 ER proteins. Analysis revealed that more than four hundred ER-resident or associated proteins were differentially regulated in invasive MDA-MB-231, many of which were linked to invasion and metastasis. Upregulated proteins were involved in cellular localization, ECM remodeling, cell mobility, adhesion, vesicle trafficking, and ER stress, whereas downregulated proteins were primarily associated with energy metabolism. Additionally, in this study, 36 ER-associated proteins were identified for the first time as candidates linked to breast cancer, highlighting their potential as novel biomarkers and therapeutic targets.</p><p><strong>Conclusion: </strong>ER-targeted TurboID proximity labelling effectively maps the proteomic landscape of breast cancer cells, revealing functional adaptations that support invasive and metastatic phenotypes. Notably, 36 ER proteins were identified as novel candidates not previously linked to breast cancer, highlighting new potential biomarkers and therapeutic targets. These findings provide valuable insights into ER proteome remodeling, offering avenues for understanding breast cancer progression and strategies to prevent metastasis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"483-502"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763304","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":"Clinical Data Analysis Identifies Prognostic Long Non-coding RNA Signatures in Lung Adenocarcinoma.","authors":"Madhur Sharma, Nidhi Chourasia, Priyanka Priyanka, Mohit Garg, Sarangadhar Nayak, Sanan Showkat Shah, Pawan Kumar Dhar, Debi Prasad Sarkar, Alo Nag, Sandeep Saxena","doi":"10.21873/cgp.20588","DOIUrl":"10.21873/cgp.20588","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and remains associated with poor clinical outcomes due to pronounced molecular heterogeneity and limited prognostic biomarkers. Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer biology, yet their systematic association with disease progression and survival in LUAD remains incompletely defined. This study aimed to identify lncRNAs that robustly associate with LUAD progression and prognosis.</p><p><strong>Materials and methods: </strong>Pre-processed lncRNA expression data for 488 LUAD tumors and 58 normal lung tissues were obtained from The Cancer Genome Atlas (TCGA) via the TANRIC platform. Following expression filtering, stage-wise differential expression analysis was performed using Welch's t-test with false discovery rate correction. Kaplan-Meier survival analysis was used to evaluate prognostic relevance. Rank-based trend analyses using Spearman correlation were conducted to assess monotonic expression changes across tumor stage, lymph-node status, and tumor size.</p><p><strong>Results: </strong>We identified 68 lncRNAs consistently upregulated across all LUAD stages relative to normal lung tissue. Survival analysis revealed that higher expression of several lncRNAs was associated with poorer overall survival. Among these, FAM83A-AS1, CYTOR, and MIR4435-2HG emerged as prominent candidates, exhibiting consistent tumor-associated overexpression and adverse survival association. Importantly, these three lncRNAs also demonstrated significant monotonic trends across increasing lymph-node involvement and primary tumor size, indicating a close association with tumor burden and disease aggressiveness.</p><p><strong>Conclusion: </strong>This integrative analysis identifies FAM83A-AS1, CYTOR, and MIR4435-2HG as robust poor-prognosis-associated lncRNAs in LUAD. Their coordinated behavior across expression, survival, nodal status, and tumor size highlights their potential utility as prognostic biomarkers and provides a framework for lncRNA-based risk stratification in lung adenocarcinoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 3","pages":"530-545"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763201","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":"Splicing Factor SF3B4 Promotes Melanoma Migration <i>via</i> Splicing-dependent Regulation of Talin1.","authors":"Seungmin Shin, Minbeom Ko, Wei Zhang, Seung Min Jeong","doi":"10.21873/cgp.20574","DOIUrl":"10.21873/cgp.20574","url":null,"abstract":"<p><strong>Background/aim: </strong>Melanoma is a highly aggressive cancer in which metastatic dissemination remains the primary cause of mortality. This study aimed to define the role of the splicing factor 3b subunit 4 (SF3B4) in melanoma progression and its downstream regulatory mechanisms.</p><p><strong>Materials and methods: </strong>SF3B4 expression was analyzed in public datasets. Its functional role was assessed by knockdown or inhibition in melanoma cells using proliferation, wound healing, and transwell assays. Talin1 expression and splicing were evaluated by RT-qPCR and immunoblotting, and FAK phosphorylation was measured as a downstream readout.</p><p><strong>Results: </strong>SF3B4 is significantly upregulated in melanoma, particularly in metastatic lesions, and its expression correlates with poor patient survival. SF3B4 depletion suppresses melanoma cell growth and migration. Talin1 was identified as a downstream target of SF3B4, as SF3B4 knockdown reduced Talin1 mRNA and protein levels and impaired its splicing, leading to increased intron retention. Consistently, SF3B4 loss reduced phosphorylation of focal adhesion kinase (FAK), indicating attenuation of Talin1-mediated signaling. Talin1 knockdown recapitulated the migration defects observed upon SF3B4 depletion, and combined knockdown showed no additive effect, supporting a shared regulatory pathway.</p><p><strong>Conclusion: </strong>SF3B4 promotes melanoma cell migration through splicing-dependent regulation of Talin1. The SF3B4-Talin1 axis represents a potential therapeutic target in metastatic melanoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"233-243"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343320","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":"Unravelling the Contribution of Matrix Metalloproteinase-3 Genotype-Phenotype to Pterygium Risk.","authors":"Hung-Chih Chen, Ning-Yi Hsia, Chung-Lin Tsai, Te-Chun Hsia, Pei-Shin Hu, Yun-Chi Wang, Hou-Yu Shih, Wen-Shin Chang, Jiunn-Cherng Lin, DA-Tian Bau, Chia-Wen Tsai","doi":"10.21873/cgp.20573","DOIUrl":"10.21873/cgp.20573","url":null,"abstract":"<p><strong>Background/aim: </strong>Pterygium is a fibrovascular ocular disease characterized by extracellular matrix (ECM) remodeling. Matrix metalloproteinase-3 (MMP-3), a key ECM-modulating enzyme, has been implicated to involved in pterygium progression, but its genetic marker has never been explored. This hospital-based case-control study investigated the association between <i>MMP-3</i> polymorphisms and pterygium risk in a Taiwanese cohort.</p><p><strong>Patients and methods: </strong>Up to five <i>MMP-3</i> genotypic patterns (rs3025058, rs522616, rs591058, rs650108, and rs679620) were identified among 160 pterygium cases and 320 age- and sex-matched controls.</p><p><strong>Results: </strong>The <i>MMP-3</i> rs3025058 5A allele was significantly associated with an elevated risk of pterygium (OR=1.94, 95%CI=1.39-2.71, <i>p</i>=0.0001). Compared to the wild-type 6A/6A genotype, individuals carrying <i>MMP-3</i> 5A/6A and 5A/5A exhibited a 1.66-fold and 4.36-fold elevated risk, respectively (<i>p</i>=0.0253 and 0.0014). Particularly, <i>MMP-3</i> rs3025058 5A/5A genotype was significantly associated with elevated pterygium risk among elder (≥60 years old) individuals (<i>p</i>=0.0003). Furthermore, transcriptional and translational analyses revealed higher MMP-3 expression in carriers of the 5A allele, with the highest levels observed in 5A/5A homozygotes (all <i>p</i><0.05). No significant associations were observed for the remaining four <i>MMP-3</i> polymorphic variants.</p><p><strong>Conclusion: </strong><i>MMP-3</i> rs3025058 may serve as a genetic biomarker for pterygium susceptibility prediction, potentially contributing to ECM dysregulation and disease progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"220-232"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343362","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":"Proteomic Signatures of Cellular Reprogramming in Bladder Cancer: Insights into the Acquisition of Cancer Stem-like States and Phenotypic Plasticity.","authors":"Bengi Su Rumeysa Barlak, Banu Iskender","doi":"10.21873/cgp.20578","DOIUrl":"10.21873/cgp.20578","url":null,"abstract":"<p><strong>Background/aim: </strong>Reprogramming somatic cells to an embryonic state opens a transformative pathway to convert cancer cells into benign ones. By delving into the changes that occur during this process, we can enhance our understanding of tumor development and unlock groundbreaking therapeutic strategies. In this study, we successfully reprogrammed the bladder cancer cell line using Yamanaka factors and conducted a stage-specific, comprehensive proteomic analysis of the resulting molecular changes.</p><p><strong>Materials and methods: </strong>The bladder cancer cell line HTB-4 was reprogrammed and cultured on vitronectin-coated surfaces following Sendai virus reprogramming, enabling a thorough evaluation of pluripotent marker expression. Both parental and reprogrammed cells were tested for proliferation, migration, invasion, and colony formation. nLC-MS/MS analysis was performed to identify molecular differences between parental bladder cancer cells and reprogrammed cells across initial passages.</p><p><strong>Results: </strong>Reprogrammed HTB-4 cells retain their ability to adhere and exhibit significant expression of pluripotency-associated proteins, forming colony-like structures. Stage-specific proteomic analyses reveal notable differences between reprogrammed cells and progenitor cells, particularly in pathways related to epithelial-mesenchymal transition, stem cell maintenance, and differentiation.</p><p><strong>Conclusion: </strong>We developed an <i>in vitro</i> model of bladder cancer reprogramming that identifies biomarkers associated with the induction of stem-like states and cellular plasticity. Our findings reveal significant stage-specific proteomic changes offering insights into the hierarchical organization of bladder cancer and the molecular mechanisms underlying the cancer stem cell phenotype. These results facilitate the development of more precise, patient-specific <i>in vitro</i> models for studying tumor recurrence and treatment resistance. However, further mechanistic studies are needed to translate effectively potential biomarkers into clinical practice.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"300-321"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343317","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}