Cancer Genomics & Proteomics最新文献

{"title":"Myxoid Pleomorphic Liposarcoma: A Review and Update.","authors":"Jun Nishio, Shizuhide Nakayama, Mikiko Aoki","doi":"10.21873/cgp.20557","DOIUrl":"10.21873/cgp.20557","url":null,"abstract":"<p><p>Myxoid pleomorphic liposarcoma (MPLPS) is an exceedingly rare and recently recognized adipocytic neoplasm that primarily occurs in children and young adults and shows a strong predilection for the mediastinum. Clinically, MPLPS demonstrates aggressive behavior and exhibits a high propensity for systemic spread and a worse overall survival. Some cases have been associated with Li-Fraumeni syndrome. Histologically, MPLPS is composed of a variable mixture of myxoid and pleomorphic liposarcoma-like components. Immunohistochemically, the tumor cells show diffuse expression of CD34 and p16 and loss of nuclear RB expression. MPLPS lacks DNA damage inducible transcript 3 (<i>DDIT3</i>) rearrangements and MDM2 proto-oncogene (<i>MDM2</i>) amplifications but shows tumor protein p53 (<i>TP53</i>) mutations and RB transcriptional co-repressor 1 (<i>RB1</i>) deletions. Moreover, recent studies have demonstrated that the most consistent molecular feature of MPLPS is genome-wide loss of heterozygosity. Surgical excision with negative margins is the mainstay of treatment for localized MPLPS. The treatment of advanced/metastatic MPLPS still poses a huge therapeutic challenge. This review provides information about the clinicoradiological features, pathogenesis, histopathology, and management currently available for MPLPS. In addition, we discuss the differential diagnosis of this novel entity.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892094","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":"Mechanistic Insights into Threonine Tyrosine Kinase Mediated Cell Cycle Regulation in Triple-negative Breast Cancer.","authors":"Siya Tang, Jiayu Zheng, Yalin Zhang, L I Zeng, Jingjing Wang, Shunshun Zhang, Youyou Chen, Qinan Yin, Xuewei Zheng","doi":"10.21873/cgp.20563","DOIUrl":"10.21873/cgp.20563","url":null,"abstract":"<p><strong>Background/aim: </strong>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking targeted therapies, characterized by high heterogeneity and poor prognosis. Dysregulated cell cycle progression and aberrant Wnt/β-catenin signaling are critical drivers of TNBC proliferation. This study aimed to advance understanding of TTK driven oncogenesis and assess its promise as a prognostic biomarker and therapeutic target in TNBC.</p><p><strong>Materials and methods: </strong>We analyzed bulk and single-cell RNA sequencing datasets to assess TTK expression and clinical relevance in breast cancer. TNBC cell lines and normal breast epithelial cells were used for <i>in vitro</i> functional assays, including cell proliferation, colony formation, migration, and cell cycle analysis following TTK knockdown with siRNA. Immunofluorescence and Western blotting evaluated TTK expression and β-catenin pathway activity. Functional enrichment, protein-protein interaction, and pseudotime trajectory analyses elucidated TTK's mechanistic roles.</p><p><strong>Results: </strong>TTK was overexpressed in breast tumors <i>versus</i> normal tissues, with elevated levels correlating with worse overall and relapse-free survival. TTK knockdown impaired TNBC cell proliferation, colony formation, and migration, and induced G₁ arrest. Single-cell analyses demonstrated TTK enrichment in cancer cells, peaking during S and G₂/M phases. Pseudotime trajectory revealed dynamic TTK upregulation during G₁-S-G₂/M transition. Mechanistically, TTK maintained β-catenin signaling and downstream Cyclin D1 expression, facilitating G₁/S entry and supporting mitotic checkpoint fidelity. Pathway enrichment analyses further confirmed TTK's centrality in cell cycle regulation and proliferative programs.</p><p><strong>Conclusion: </strong>TTK drives TNBC progression by orchestrating G₁/S and G₂/M transitions and sustaining β-catenin-Cyclin D1 signaling. Its restricted expression in normal tissues, combined with oncogenic effects, positions TTK as a promising prognostic biomarker and therapeutic target. Pharmacological inhibition of TTK, potentially combined with β-catenin pathway inhibitors, may offer an effective strategy for TNBC treatment.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"93-108"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892058","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":"Exosomes Transfer ST6GAL1-mediated Therapeutic Resistance in Rectal Cancer Cells.","authors":"Jeremie M P Lever, Regina K Irwin, Vivek Somasundaram, Yuwei Song, Chandler M McLeod, Mary Smithson, Gregory Williams, Zechen Chong, Karin M Hardiman","doi":"10.21873/cgp.20558","DOIUrl":"10.21873/cgp.20558","url":null,"abstract":"<p><strong>Background/aim: </strong>Locally advanced Rectal cancer (RC) is treated with neoadjuvant chemoradiation, but treatment resistance is common. We have previously shown that ST6GAL1 causes RC chemoradiation resistance. Exosomes are small particles that can transfer proteins between cells. We hypothesized that exosomes transfer ST6GAL1 between RC cells, spreading treatment resistance.</p><p><strong>Materials and methods: </strong>We characterized exosomes isolated from multiple ST6GAL1-expressing colorectal cancer (CRC) cell lines. Treatment response was assessed in ST6GAL1-knockdown (KD) cells treated with these exosomes. Single cell RNA sequencing (scRNA-seq) and flow cytometry for surface sialylation were performed on CRC organoids to compare presence of ST6GAL1 RNA and protein activity.</p><p><strong>Results: </strong>Exosomes from multiple CRC cell lines contained ST6GAL1 protein and ST6GAL1 KD cells treated with these exosomes demonstrated transfer of ST6GAL1 with increase in protein in treated cells, but not mRNA, and the protein localized to the Golgi complex. In addition, treated cells demonstrated increased resistance to chemoradiation-induced apoptosis (<i>p</i>=0.02, n=4) and increased colony formation after treatment (<i>p</i>=0.01, n=4). Single cell sequencing revealed that only 16 percent of cells have ST6GAL1 mRNA but 86 percent have evidence of ST6GAL1 protein activity.</p><p><strong>Conclusion: </strong>These findings demonstrate that ST6GAL1-containing rectal cancer exosomes transfer ST6GAL1 between cells causing treatment resistance.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"12-26"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892053","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":"Comparative Transcriptomic Analysis Identifies Predictive Biomarkers of Pathological Complete Response in Triple-negative Breast Cancer.","authors":"Fang-Ming Chen, Chung-Liang Li, Mei-Ren Pan, Yun-Cian Huang, Li-Ju Huang, Sin-Hua Moi, Shu-Jyuan Chang, Ping-Fu Yang, Chieh-Ni Kao, Jung-Yu Kan, Li-Kun Ko, Hidenobu Takahashi, Chia-Yu Kuo, Shen-Liang Shih, Ming-Feng Hou, Yi-Hsiung Lin, Chi-Wen Luo","doi":"10.21873/cgp.20561","DOIUrl":"10.21873/cgp.20561","url":null,"abstract":"<p><strong>Background/aim: </strong>Pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) is a strong prognostic indicator in triple-negative breast cancer (TNBC). However, reliable predictive biomarkers for pCR remain limited. This study aimed to identify gene expression signatures associated with pCR in TNBC to facilitate more precise treatment stratification.</p><p><strong>Materials and methods: </strong>Tumor samples from 16 TNBC patients treated with NAC at the Kaohsiung Medical University Hospital (KMUH) were analyzed, including 5 pCR and 11 non-pCR cases. RNA sequencing (RNA-seq) was performed, and differentially expressed genes (DEGs) were identified using DESeq2 (|log₂FC| ≥2, adjusted <i>p</i><0.05). Gene expression profiles were compared with a validation cohort of 27 NAC-responsive TNBC cases from The Cancer Genome Atlas (TCGA). Overlapping DEGs were identified using Venn diagram analysis, and drug-gene interaction databases were queried to explore therapeutic relevance.</p><p><strong>Results: </strong>In the KMUH cohort, 175 DEGs were identified, including 146 up-regulated and 29 down-regulated genes in non-pCR tumors. Fifteen DEGs demonstrated consistent differential expression patterns between KMUH and TCGA datasets, showing enrichment in pCR samples. These genes may serve as predictive biomarkers for NAC response. Notably, several of these genes are potentially druggable, suggesting opportunities for targeted therapy in chemoresistant TNBC.</p><p><strong>Conclusion: </strong>We identified and validated a 15 gene signature associated with pCR in TNBC across independent cohorts. These findings offer a promising basis for improving patient stratification, guiding treatment decisions, and developing targeted therapies for NAC-resistant TNBC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"66-80"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892078","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":"Corrigendum.","authors":"","doi":"10.21873/cgp.20568","DOIUrl":"https://doi.org/10.21873/cgp.20568","url":null,"abstract":"","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"155"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892074","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":"Mutational Spectrum of T-Cell Large Granular Lymphocytic Leukemia: Insights From the AACR Project GENIE Consortium.","authors":"Bhanu Surabi Upadhyayula, Grace S Saglimbeni, Edie Gobel, Abbi Gobel, Tyson J Morris, Akaash Surendra, Beau Hsia, Akshat Sood, Abubakar Tauseef","doi":"10.21873/cgp.20566","DOIUrl":"10.21873/cgp.20566","url":null,"abstract":"<p><strong>Background/aim: </strong>T-cell large granular lymphocyte leukemia (T-LGLL) is a rare, indolent lymphoproliferative disorder of cytotoxic T cells in the peripheral blood, bone marrow, and spleen. This analysis was conducted to characterize genomic alterations and highlight potential therapeutic targets, with the goal of refining the molecular landscape of T-LGLL by emphasizing population-specific biomarkers.</p><p><strong>Materials and methods: </strong>This study utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database to identify common gene mutations. Using the AACR GENIE database, a retrospective analysis of T-cell large granular lymphocyte leukemia (T-LGLL) samples was performed. The data was evaluated by extracting patient demographics and excluding synonymous mutations from consideration. Statistical significance was assessed using chi-squared tests and computational analyses in RStudio (R Foundation for Statistical Computing, Boston, MA, USA). Somatic mutations and chromosomal copy number variations were evaluated, with statistical significance defined as <i>p</i>=0.001.</p><p><strong>Results: </strong>Frequently observed somatic mutations included <i>STAT3</i> (41.7%), <i>STAT2</i> (20.9%), <i>KMT2D</i> (11.3%), <i>SETD1B</i> (8.7%), <i>TP53</i> (7.0%), <i>TNFAIP3</i> (6.1%), <i>DNMT3A</i> (5.2%), <i>FAS</i> (4.3%), <i>SMARCA4</i> (3.5%), <i>EPHB1</i> (2.6%), <i>KSR2</i> (2.6%), <i>ALOX12B</i> (2.6%), <i>EGFR</i> (2.6%), <i>DDX3X</i> (7.0%), and <i>IKZF3</i> (1.7%). When stratified by demographic variables, males and White patients demonstrated a higher frequency of mutations.</p><p><strong>Conclusion: </strong>This study provides a comprehensive genomic profile of T-LGLL, identifying recurrent somatic mutations and commonly affected pathways. Notably, frequent alterations were observed in the <i>FAS</i>-<i>FASL</i> signaling pathway, underscoring its potential as a target for therapeutic development.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"135-143"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892017","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":"Optimizing Liquid Biopsy: Spike-In Panel Approach for ctDNA Copy Number Variation Analysis.","authors":"Hyunji Kim, Byoung Mok Kim, Jinho Kim, Soo Hyun Seo, Sang Mee Hwang, Kyoung Un Park","doi":"10.21873/cgp.20565","DOIUrl":"10.21873/cgp.20565","url":null,"abstract":"<p><strong>Background/aim: </strong>Circulating tumor DNA (ctDNA) testing has emerged as a minimally invasive tool for precision oncology, enabling dynamic monitoring of tumor burden and treatment response. However, commercial ctDNA NGS assays often omit clinically important oncogenes, limiting accurate assessment of copy-number variation (CNV). Amplifications of <i>MYC</i> and <i>MYCN</i> are key drivers of tumor progression and therapeutic resistance, and their detection is required under the Korean National Health Insurance coverage criteria. We evaluated whether a custom spike-in panel added to the Avenio ctDNA Expanded Kit improves CNV detection for <i>MYC</i> and <i>MYCN</i> to meet these clinical and regulatory requirements.</p><p><strong>Materials and methods: </strong>Spike-in targets were designed with KAPA Target Enrichment Custom Designs and integrated into the Avenio panel. Reference materials (Horizon Structural Multiplex cfDNA Standard, 5% (<i>MYCN</i> ≈9.5 copies); Seraseq ctDNA Complete, 1% (<i>MYC</i>≈3.07 copies)) were measured in triplicate; Seraseq was additionally diluted 1:2 and 1:10. Eight cancer-free plasma samples established the baseline. Libraries were sequenced on a NextSeq 550Dx (high-output). CNV analysis used CNVkit v0.9.9 with custom parameters (reference spread threshold increased 1.0→1.5; GC upper limit relaxed 0.7→0.8, lower limit retained at 0.3). Log2 fold-change <i>versus</i> healthy controls assessed CNV signals.</p><p><strong>Results: </strong>Mean exon coverage was 698.5 for <i>MYCN</i> (range=325.4-1081.2) and 740.3 for <i>MYC</i> (range=438.8-1221.7). In the Horizon material, all <i>MYCN</i> exons showed ≥3.6-fold change (mean 4.2; inferred CNV ≈8.2), concordant with expected amplification. Seraseq showed a mean <i>MYC</i> fold change of 1.46 (inferred CNV ≈2.94); diluted samples yielded CNV estimates of 2.79 (1:2) and 2.67 (1:10), indicating limited sensitivity below ~3 copies. One <i>MYC</i> exon reproducibly underperformed despite adequate coverage.</p><p><strong>Conclusion: </strong>Incorporation of a spike-in panel into the Avenio ctDNA assay enabled reliable detection of high-level <i>MYC</i>/<i>MYCN</i> amplifications and fulfilled practical requirements for local reimbursement. The estimated CNV limit of detection in this setting is ≈3 copies. Further replicate testing and validation with clinical specimens are warranted to refine sensitivity and interlaboratory robustness.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"127-134"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892159","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":"Prognostic Implications of Exosomal miRNA Networks Regulating TGFβ1-induced Epithelial-Mesenchymal Transition Signature in Oral Squamous Cell Carcinoma.","authors":"Minjeong Kim, Su Il Kim, Young-Gyu Eun, Nakwon Choi, Junbeom Kim, Young Chan Lee","doi":"10.21873/cgp.20560","DOIUrl":"10.21873/cgp.20560","url":null,"abstract":"<p><strong>Background/aim: </strong>Oral squamous cell carcinoma (OSCC) prognosis is often poor due to metastasis driven by the epithelial-mesenchymal transition (EMT), creating a need for biomarkers that reflect this process. Exosomal microRNAs (miRNAs) secreted by cancer cells regulate EMT, but their complex, network-level interactions are poorly understood. This study aimed to identify a prognostic gene signature by analyzing the exosomal miRNA network from a TGFβ1-induced EMT cell model and validating its clinical relevance in a patient cohort.</p><p><strong>Materials and methods: </strong>A TGFβ1-induced EMT model was established in OSCC cells and the exosomal miRNAs from their conditioned media was profiled using microarrays. A 43-gene signature was developed based on the collective targets of the EMT-regulated miRNA network. The prognostic significance of this signature was then validated in The Cancer Genome Atlas (TCGA) OSCC patient cohort (n=315) using hierarchical clustering and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>The analysis identified an Exo-miR EMT signature comprising miRNAs that collectively regulate EMT-associated gene networks. Using this signature, hierarchical clustering successfully stratified patients into two distinct subgroups with different prognoses. Kaplan-Meier analysis revealed that the high-risk group had a significantly poorer overall survival than the low-risk group (<i>p</i>=0.02). Multivariate analysis confirmed that the Exo-miR EMT signature was an independent prognostic factor for OSCC.</p><p><strong>Conclusion: </strong>EMT-related gene networks regulated by exosomal miRNAs carry clinically meaningful information about tumor aggressiveness in OSCC. The derived Exo-miR EMT signature offers biologically grounded risk stratification that complements conventional clinicopathological factors and supports further development of exosome-based liquid biopsies for prognostic assessment in OSCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"50-65"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892129","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":"RUNX2 Represses the EWS-FLI1-mediated Transcription in Ewing's Sarcoma Cells.","authors":"Takao Kitagawa, Byron Baron, Hajime Okita, Junichi Hamada, Koji Nakagawa, Masanobu Kobayashi, Tohru Ohta, Yasuhiro Kuramitsu","doi":"10.21873/cgp.20559","DOIUrl":"10.21873/cgp.20559","url":null,"abstract":"<p><strong>Background/aim: </strong>Ewing's sarcoma is an aggressive pediatric malignancy driven by specific chromosomal translocations, predominantly leading to the oncogenic fusion protein EWS-FLI1. Runt-related transcription factors 1 and 2 (RUNX1 and RUNX2), which are key transcription factors involved in osteoblastic differentiation and skeletal morphogenesis, are not expressed in Ewing's sarcoma. Our study aimed to elucidate the relationship between the <i>RUNX</i> genes and EWS-FLI1.</p><p><strong>Materials and methods: </strong>We used Ewing's sarcoma cell lines (A673 and NCR-EW2). EWS-FLI1 knockdown was achieved using shRNA, while inducible expression of <i>RUNX1, RUNX2, EWS-FLI1</i>, or <i>EWS-ERG</i> was performed using a Tet-on system. Gene and protein expression levels were quantitatively assessed by qPCR and Western blot analysis, respectively. Cell growth was evaluated using spheroid formation and cell viability assays. Truncated RUNX1 or RUNX2 constructs were employed to identify functional domains, with their intracellular localization confirmed by immunostaining.</p><p><strong>Results: </strong>We observed low expression of RUNX1 and RUNX2 in Ewing's sarcoma cells. Notably, EWS-FLI1 knockdown increased <i>RUNX2</i> gene expression. Conversely, inducible expressions of either <i>RUNX1</i> or <i>RUNX2</i> suppressed the expression of EWS-FLI1 target genes and inhibited cell proliferation and spheroid formation. Additionally, the RUNT domain of RUNX1 and RUNX2 was not essential for their inhibitory effect on EWS-FLI1 target gene expression. Importantly, both EWS-FLI1 and EWS-ERG down-regulated <i>RUNX2</i> gene expression in hTert-RPE1 cells.</p><p><strong>Conclusion: </strong>EWS-FLI1 suppresses <i>RUNX2</i> gene expression in Ewing's sarcoma cells, and re-expressing <i>RUNX2</i> inhibits cell growth. These findings suggest that RUNX2 has a negative impact on the oncogenic process in Ewing's sarcoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"27-49"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892157","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":"Augmenter of Liver Regeneration Enhances Hepatocellular Carcinoma Cell Growth Through COX-2-associated Signaling.","authors":"L I Li, Jing Cheng, Hong-Li Guo, Q I Liu, N A Wang, Chuan-Xin Wu, Hang Sun","doi":"10.21873/cgp.20564","DOIUrl":"10.21873/cgp.20564","url":null,"abstract":"<p><strong>Background/aim: </strong>The expression of augmenter of liver regeneration (ALR), a potent growth factor, is significantly up-regulated in hepatocellular carcinoma (HCC). This study aims to investigate the potential functions and mechanisms of ALR in HCC.</p><p><strong>Materials and methods: </strong>ALR expression in Huh7 cells was silenced using an RNA interference (RNAi) lentiviral vector, and differentially expressed genes (DEGs) were identified through DNA microarray analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to explore the functional roles and mechanisms of ALR in HCC. A protein-protein interaction (PPI) network was constructed based on the identified DEGs, and hub genes with high connectivity were identified. The relationship between these hub genes, ALR, and HCC cell proliferation was further analyzed.</p><p><strong>Results: </strong>A total of 299 DEGs were identified, including 171 up-regulated and 128 down-regulated genes. GO, KEGG, and GSEA analyses revealed that ALR is closely associated with receptor protein signaling pathways, cell proliferation, metabolism, mitochondrial homeostasis, and cell migration. Furthermore, ALR expression was associated with the enrichment of oncogenic pathways, including KRAS, Hedgehog, and IL-6/JAK/STAT3 signaling. Analysis of the PPI network and hub gene analysis identified Cyclooxygenase-2 [COX-2, also known as prostaglandin-endoperoxide synthase 2 (PTGS2)] as a key hub gene, which was selected for further investigation. Real-time quantitative PCR and Western blot results indicated that COX-2 is a downstream target of ALR. Additionally, ALR was shown to promote Huh7 cell proliferation by regulating COX-2.</p><p><strong>Conclusion: </strong>These findings connect ALR to the dysregulation of multiple oncogenic signaling pathways in HCC. Additionally, ALR may promote the proliferation of HCC by modulating the downstream pro-inflammatory factor COX-2, suggesting that ALR could serve as a potential therapeutic target for HCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"109-126"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892098","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}