Cancer Genomics & Proteomics最新文献

{"title":"EPS8 Differentially Regulates Antioxidant Defense and Mitochondrial Homeostatic Signaling in LNCaP and Enzalutamide-resistant LNCaP Cells.","authors":"Sih-Han Chen, Chun-Hsien Wu, Pei-Fang Hsieh, Wen-Chi Huang, Yu-Lin Yang, Victor C Lin, Ming-Wei Lin","doi":"10.21873/cgp.20611","DOIUrl":"10.21873/cgp.20611","url":null,"abstract":"<p><strong>Background/aim: </strong>Epidermal growth factor receptor pathway substrate 8 (EPS8) is an adaptor protein implicated in tumor progression and therapeutic resistance; however, its role in mitochondrial homeostatic signaling and antioxidant regulation remains unclear. This study examined the effects of EPS8 modulation in lymph node carcinoma of the prostate (LNCaP) and enzalutamide-resistant LNCaP (LNCaP-Enz) cells.</p><p><strong>Materials and methods: </strong>LNCaP-Enz cells were generated by long-term exposure to enzalutamide and maintained in 5 μM enzalutamide. EPS8 expression was modulated by plasmid-mediated overexpression or shRNA-mediated knockdown. Superoxide dismutase (SOD) activity and cellular adenosine triphosphate (ATP) levels were measured using colorimetric assays. Mitochondrial membrane potential (ΔΨm) was evaluated using JC-1 fluorescence, and mitochondrial staining patterns were qualitatively examined using MitoTracker Green staining. Protein expression associated with antioxidant defense, mitochondrial dynamics, mitochondrial stress response, mitochondrial biogenesis, and AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling was analyzed by western blotting.</p><p><strong>Results: </strong>EPS8 overexpression increased SOD activity and the expression of SOD1 and SOD2, whereas EPS8 knockdown reduced these antioxidant parameters. Conversely, EPS8 silencing increased cellular ATP levels and enhanced JC-1 red fluorescence patterns. EPS8 silencing increased MFN1 and OPA1 expression and reduced DRP1 expression, consistent with a fusion-associated mitochondrial profile. EPS8 silencing also increased SIRT1, PGC-1α, NRF1, TFAM, p-AMPK/AMPK, and p-mTOR/mTOR, but reduced HSP60, LONP1, ATF5, and CEBPβ expression.</p><p><strong>Conclusion: </strong>EPS8 differentially regulates SOD-associated antioxidant capacity and mitochondrial homeostatic signaling in LNCaP-based cell models. Further studies are required to determine whether EPS8 modulation affects enzalutamide responsiveness.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 5","pages":"964-981"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863170","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":"Multi-omics Investigations of Immune Microenvironment of Human Colorectal Cancer.","authors":"Hongwei Zeng, Liewen Lin, Yumei Chen, Ligang Xia, Donge Tang, Yong Dai, Wei Zhang","doi":"10.21873/cgp.20614","DOIUrl":"10.21873/cgp.20614","url":null,"abstract":"<p><strong>Background/aim: </strong>Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Although immunotherapy has improved outcomes for a subset of patients, its limited efficacy in many cases highlights the need for a more comprehensive understanding of the CRC immune microenvironment. This study aimed to characterize the molecular landscape of the CRC immune microenvironment using an integrated multi-omics approach and to identify candidate regulatory molecules associated with immune remodelling.</p><p><strong>Materials and methods: </strong>We integrated structural variation, DNA methylation, chromatin accessibility, proteomic, and phosphoproteomic data generated from an in-house CRC cohort with transcriptomic data from The Cancer Genome Atlas (TCGA). Analyses focused on 1,539 immune-related genes (IRGs) associated with CD4⁺ T cells, B cells, and natural killer (NK) cells. Multi-layered genomic and proteomic analyses were performed to identify altered immune-related pathways, hub genes, candidate transcription factors, and upstream kinases.</p><p><strong>Results: </strong>Higher infiltration of CD4⁺ T cells, B cells, and NK cells was associated with CRC. IRGs exhibited widespread alterations across genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic levels. IL10, LEP, ITGAM, and EGFR emerged as candidate hub genes. EGFR phosphorylation at S991 and T693 was significantly decreased in CRC. STAT2 and HSF1 were identified as candidate upstream transcription factors, while CDK2 emerged as a candidate upstream kinase associated with immune infiltration and immune checkpoint expression.</p><p><strong>Conclusion: </strong>This study provides a systematic multi-omics characterization of immune microenvironment remodelling in CRC and identifies candidate molecular regulators that may serve as potential targets for future immunotherapy research.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 5","pages":"1021-1042"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863411","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":"Genetic Insights into Interleukin-13 Polymorphisms in Colorectal Cancer Risk and Progression.","authors":"Te-Cheng Yueh, Tao-Wei Ke, Jiaqi Wang, Yang Deng, Yi-Chih Hung, Cheng-Wei Huang, Yu-Chen Chang, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, DA-Tian Bau","doi":"10.21873/cgp.20597","DOIUrl":"10.21873/cgp.20597","url":null,"abstract":"<p><strong>Background/aim: </strong>Colorectal cancer (CRC) is a major global health burden with increasing incidence and significant mortality, particularly in advanced stages. Genetic susceptibility and inflammation-related pathways, including cytokine signaling, are increasingly recognized as key contributors to CRC pathogenesis. Interleukin-13 (IL-13) polymorphisms, particularly rs1800925 and rs20541, have been implicated in cancer biology; however, their roles in CRC remain inconclusive.</p><p><strong>Materials and methods: </strong>A hospital-based case-control study was conducted in Taiwan, including 362 CRC patients and 362 age- and sex-matched controls. Genomic DNA was extracted from peripheral blood, and <i>IL-13</i> rs1800925 and rs20541 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. Associations between genotypes and CRC risk and clinicopathological features were estimated using odds ratios (ORs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>The genotype distributions of rs1800925 and rs20541 in controls conformed to the Hardy-Weinberg equilibrium (<i>p</i>=0.2098 and 0.7888, respectively). No overall significant associations were observed between <i>IL-13</i> polymorphisms and CRC susceptibility. For rs1800925, the CT and TT genotypes showed ORs of 1.20 (95%CI=0.88-1.65, <i>p</i>=0.2772) and 1.42 (95%CI=0.80-2.54, <i>p</i>=0.2844), respectively. For rs20541, the AG and AA genotypes exhibited ORs of 1.11 (95%CI=0.82-1.51, <i>p</i>=0.5581) and 1.21 (95%CI=0.74-1.98, <i>p</i>=0.5185). However, rs1800925 CT+TT genotypes were associated with significantly increased risk of distant metastasis at diagnosis (OR=2.12, 95%CI=1.40-3.20, <i>p</i>=0.0005), while rs20541 AG+AA genotypes were associated with advanced stage (OR=1.50, 95%CI=1.03-2.19, <i>p</i>=0.0423) and metastatic disease at diagnosis (OR=2.16, 95%CI=1.39-3.36, <i>p</i>=0.0007).</p><p><strong>Conclusion: </strong>Although <i>IL-13</i> rs1800925 and rs20541 polymorphisms are not associated with CRC susceptibility, they may be associated with clinicopathological aggressiveness at diagnosis, highlighting their potential utility in stratifying CRC severity, particularly in the Taiwanese population.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"701-713"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350954","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 and Functional Significance of p38δ (MAPK13) in Lung Cancer.","authors":"Mehek Sumar, Timothy P Fleming, Ross M Bremner, Narendra V Sankpal","doi":"10.21873/cgp.20595","DOIUrl":"10.21873/cgp.20595","url":null,"abstract":"<p><strong>Background/aim: </strong>MAPK13 (p38δ) is a frequently identified but often ignored MAP kinase in epithelial gene signatures. This study aimed to characterize p38δ expression in normal and cancerous epithelial tissues, investigate its possible role in epithelial identity, epithelial-mesenchymal transition (EMT), cancer progression, drug resistance, and evaluate its prognostic value.</p><p><strong>Materials and methods: </strong>Quantitative analysis assessed p38δ expression across diverse normal human epithelial tissues and correlated it with epithelial markers in cancer cell lines. A p38δ gene signature was analyzed for pathway enrichment in epithelial processes. p38δ expression was compared between epithelial and mesenchymal lung cancer models and in EGFR inhibitor-resistant cells. Prognostic data on cancer patient survival was collected for various cancer types. Functional studies included p38δ knockdown to evaluate EMT markers, E-cadherin/EpCAM, Vimentin and proliferation, and exogenous p38δ expression to assess cell growth/migration. p38δ mRNA and protein levels were measured in Osimertinib-resistant cell lines.</p><p><strong>Results: </strong>p38δ was predominantly expressed across diverse normal epithelial tissues and correlated strongly with epithelial markers in cancer cells. Its gene signature enriched pathways vital for epithelial architecture, adhesion, and differentiation. p38δ was consistently higher in epithelial-enriched lung cancer models and suppressed in EGFR inhibitor-resistant cells. Prognostic impact was context-dependent: high expression correlated with favorable overall survival in ovarian, lung, and rectum cancers, but inversely with outcomes in liver, breast, and pancreatic cancers. Functionally, p38δ knockdown induced EMT and increased proliferation. Conversely, exogenous p38δ suppressed cell growth/migration. Crucially, acquired Osimertinib resistance consistently corresponded with significant reductions in p38δ levels.</p><p><strong>Conclusion: </strong>p38δ is a critical marker and regulator of epithelial identity. Its dysregulation and loss are systematically linked to EMT and drug resistance in cancer. Given its complex, context-dependent prognostic value and functional significance, p38δ holds significant potential as a therapeutic target.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"664-685"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350931","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":"IL1B-Expressing Exhausted CD4⁺ T Cells Are Associated With Disease Aggressiveness in Glioblastoma.","authors":"Jinshan Wang, A O Zhu, Jian Wang, Bin Hu, Kashif Rafiq Zahid, Ailiang Zeng, Yiheng Tan, Jia Yang","doi":"10.21873/cgp.20599","DOIUrl":"10.21873/cgp.20599","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastomas (GBMs) are aggressive primary brain tumors characterized by immune evasion and therapeutic resistance. Here, we aimed to decipher the transcriptional landscape of disease aggressiveness in GBM by employing a multi-layered transcriptomic approach.</p><p><strong>Materials and methods: </strong>We performed transcriptome-wide differential expression analysis using TCGA IDH-wildtype GBM data after stratifying the tumors based on epithelial-mesenchymal transition (EMT) signature scores. Functional and pathway enrichment analyses, STRING-based protein-protein interaction (PPI) network assisted with centrality and random-walk analyses, univariate and multivariate Cox survival analyses, Gene Set Enrichment Analysis (GSEA), single-cell RNA (scRNA) sequencing analysis, CIBERSORTx immune deconvolution, and T cell exhaustion profiling were performed. Key findings were validated in independent datasets.</p><p><strong>Results: </strong>We identified 2088 protein-coding genes associated with disease aggressiveness in GBM. Among 1070 upregulated genes, 432 were risk-associated and enriched for immune-inflammatory pathways. Network analysis identified IL1B and CD4 as top hub genes, both of which were independently prognostic for poor overall survival. scRNA-seq analysis attributed CD4 expression to tumor-infiltrating T cells, more than half of which also co-expressed IL1B. CIBERSORTx deconvolution suggested progressive accumulation and exhaustion of CD4⁺ T memory resting cells and Tregs along disease aggressiveness. CCL5 is preferentially expressed by tumor cells, whereas CCR1 and CCR5 by CD4⁺ T cells, supporting a CCL5-CCR1/CCR5-associated recruitment pattern. IL1B correlates with accumulation of exhausted CD4⁺ T memory cells and aligns with enrichment of disease aggressiveness and inflammatory signatures. IL1R1/NF-κB-related transcriptional targets downstream are coordinately upregulated in tumors having high EMT scores and high IL1B expression.</p><p><strong>Conclusion: </strong>CD4⁺ T cells are recruited to GBM tumors preferentially <i>via</i> the CCL5-CCR1/CCR5 axis, where their exhaustion-related IL1B upregulation along disease progression aligns with mesenchymal reprogramming that hallmarks disease aggressiveness in IDH-wildtype GBM.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"730-754"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350923","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":"Glucose and Glutamine Define Independent Activation-Braking Metabolic States in Triple Negative Breast Cancer Cells.","authors":"Elizabeth A Mazzio, Renee Reams, Ramesh B Badisa, Jean Baptiste Lamango, Zonelle Hanley, Karam F A Soliman","doi":"10.21873/cgp.20593","DOIUrl":"10.21873/cgp.20593","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer metabolism is often viewed as a cooperative reliance on glucose and glutamine; however, whether these nutrients can enforce discrete, non-overlapping metabolic states remains unclear. This study aimed to isolate nutrient-specific regulatory programs.</p><p><strong>Materials and methods: </strong>MDA-MB-231 human breast cancer cells were cultured under four distinct metabolic environments: glucose/glutamine nutrient-repleted (fed), dual glucose/glutamine deficiency, and isolated repletion of either glucose or glutamine. Groups were evaluated for integrated transcriptomic, metabolomic, and lipidomic profiles to identify only the non-redundant, nutrient-enforced architectures.</p><p><strong>Results: </strong>The data show a mutually restrictive mechanistic state. Glutamine functions as a metabolic architect, restoring glycolytic enzyme transcripts (without lactate production), while inducing PDK1/3 which would decouple glycolysis from the TCA cycle. These changes are concomitant with a glutamine flux toward reductive TCA-driven lipogenesis, citric acid overflow, sterol synthesis (SREBF1/2), structural membrane expansion (phospholipids/sphingolipids) and the unique production of alanine as a nitrogen pool, independent of glycolytic flux. Conversely, glucose alone acts as the executor, licensing chromatin engagement, DNA replication, and mitotic progression. Glucose alone resolved ER stress, restored hexose-phosphate-derived glycosylation (mannose-6-phosphate), enabled lactic acid production, and diverted excess carbon into a triglyceride storage pool (>40% of lipids). Notably, each nutrient suppressed core elements of the other's program, revealing a reciprocal activation-braking system. Interestingly, ATP yield from glucose or glutamine alone were comparable, but not arbitrary; instead, aligned with the functional state of the cell. Glucose alone supported glycolytic phosphorylation and proliferative execution, as marked by lactate accumulation, whereas glutamine alone supported Krebs cycle-related phosphorylation, characterized by citrate accumulation and the maintenance of cellular structure and membrane infrastructure.</p><p><strong>Conclusion: </strong>Glucose and glutamine enforce a balance of two independent, reciprocally regulated metabolic states. This data provides a systems-level explanation for metabolic resilience in cancer and may lead to the identification of nutrient-specific targets for combination therapy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"629-648"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350891","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":"<i>NOX4</i> Shapes Inflammatory Microenvironment and Predicts Prognosis and Therapeutic Response in Gastric Cancer.","authors":"Deming Li, Jianan Zhou, L I Feng","doi":"10.21873/cgp.20600","DOIUrl":"10.21873/cgp.20600","url":null,"abstract":"<p><strong>Background/aim: </strong>The inflammatory microenvironment plays a critical role in stomach adenocarcinoma (STAD); however, the clinical relevance of inflammation-related genes remains unclear. This study aimed to identify key inflammation-related hub genes and evaluate their prognostic, immunological, and therapeutic significance in STAD.</p><p><strong>Materials and methods: </strong>This study integrated six transcriptomic datasets from GEO and TCGA databases to identify differentially expressed genes (DEGs) between STAD and normal tissues. Inflammation-related DEGs were enriched using the MSigDB hallmark gene set, followed by protein-protein interaction (PPI) network analysis to identify hub genes. The expression, diagnostic value, prognostic significance, immune microenvironment associations, and drug sensitivity of the key hub gene, <i>NOX4</i>, were comprehensively evaluated using TCGA clinical data and diverse bioinformatics platforms.</p><p><strong>Results: </strong><i>NOX4</i> was identified as a significantly overexpressed inflammation-related hub gene in STAD, correlating with <i>Helicobacter pylori</i> infection and advanced pathological staging. High <i>NOX4</i> expression predicted a poor prognosis. A nomogram integrating <i>NOX4</i> expression, age, and T stage achieved AUC values of 0.730, 0.719, and 0.706 for 1-, 3-, and 5-year overall survival, respectively. Functional enrichment revealed <i>NOX4</i>'s involvement in pathways such as cytoskeletal organization and ECM-receptor interactions. Immunologically, high <i>NOX4</i> expression correlated with increased M2 macrophage infiltration, decreased memory B cells and resting CD4+ memory T cells, and higher TIDE scores, suggesting potential immunotherapy resistance. Mutation analysis showed distinct high-frequency mutations (<i>e.g., TP53, TTN</i>) associated with <i>NOX4</i> levels. Furthermore, drug sensitivity analysis indicated that high <i>NOX4</i> expression was linked to higher IC₅₀ values for 14 chemotherapeutic agents, including cisplatin and sorafenib, indicating potential chemoresistance.</p><p><strong>Conclusion: </strong><i>NOX4</i> emerges as a key regulator of the STAD inflammatory microenvironment and a robust prognostic biomarker. Its role in immune modulation and chemoresistance provides novel insights for developing precision therapeutic strategies in STAD.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"755-776"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350847","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":"NRF1 Activates the AMPK/SIRT1/PGC-1α/TFAM Axis to Suppress EMT and Tumor Progression in Lung Adenocarcinoma.","authors":"Hsing-Hsien Wu, Pei-Fang Hsieh, Ming-DER Shi, Chun-Hung Ko, Chun-Hsien Wu, Victor C Lin, Shu-Fen Liu, Yu-Ju Hung, Tzu-Sui Hung, I-Chou Wang, Yu-Lin Yang","doi":"10.21873/cgp.20602","DOIUrl":"10.21873/cgp.20602","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung cancer is the leading cause of cancer-related mortality globally, emphasizing the need for identifying molecular mechanisms that drive its progression and therapeutic resistance. Nuclear respiratory factor 1 (NRF1) is a transcription factor involved in mitochondrial biogenesis, apoptosis, and epithelial-mesenchymal transition (EMT), all of which contribute to cancer initiation and metastasis. This study investigated the role of NRF1 in lung cancer progression and its potential as a therapeutic target.</p><p><strong>Materials and methods: </strong>A549 lung adenocarcinoma cells were used to evaluate the effects of NRF1 overexpression (pcDNA-NRF1) and silencing (shRNA-NRF1). Moreover, western blotting were used to assess EMT markers (E-cadherin, N-cadherin, vimentin), mitochondrial biogenesis factors (T-fam), and apoptotic markers (caspase-3, caspase-9). Functional assays were performed to measure cell migration, and apoptosis. SCID mice implanted with NRF1-modified tumors were used for <i>in vivo</i> validation. Statistical analyses included analysis of variance (<i>p</i><0.05).</p><p><strong>Results: </strong>NRF1 overexpression increased E-cadherin while reducing N-cadherin and vimentin, inhibiting EMT. It suppressed cell migration while enhancing mitochondrial biogenesis and apoptosis, as indicated by elevated caspase-3 and caspase-9 activity. Conversely, NRF1 silencing promoted EMT, reduced mitochondrial biogenesis, and decreased apoptosis. <i>In vivo</i>, NRF1-overexpressing tumors exhibited higher levels of E-cadherin, T-fam, and caspase-3, supporting NRF1's role in EMT suppression and mitochondrial and apoptotic pathway enhancement.</p><p><strong>Conclusion: </strong>NRF1 acts as a suppressor of EMT and a promoter of mitochondrial biogenesis and apoptosis in lung cancer. Its regulatory role suggests NRF1 as a potential therapeutic target for inhibiting tumor progression and overcoming resistance to conventional therapies.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"806-823"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350704","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":"Analysis of Formimidoyltransferase Cyclodeaminase as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer.","authors":"Kenshiro Tanaka, Shinichi Umeda, Norifumi Hattori, Takayoshi Kishida, Koki Nakanishi, Haruyoshi Tanaka, Dai Shimizu, Hideki Takami, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera","doi":"10.21873/cgp.20596","DOIUrl":"10.21873/cgp.20596","url":null,"abstract":"<p><strong>Background/aim: </strong>Formimidoyltransferase cyclodeaminase (<i>FTCD</i>) is a folate-metabolizing enzyme involved in histidine catabolism and intracellular folate homeostasis. Although <i>FTCD</i> has been implicated in cancer progression and epithelial-mesenchymal transition (EMT) in several malignancies, its oncological role in colorectal cancer (CRC) remains unclear. This study investigated the biological and clinical significance of <i>FTCD</i> in CRC.</p><p><strong>Materials and methods: </strong><i>FTCD</i> expression was evaluated in CRC cell lines and clinical specimens from 301 patients with resectable stage II/III CRC who underwent curative resection. Functional analyses, including proliferation, invasion, migration, and subcutaneous xenograft assays, were performed using small interfering RNA-mediated <i>FTCD</i> knockdown. Associations between <i>FTCD</i> expression and clinicopathological factors, recurrence patterns, disease-free survival (DFS), and overall survival (OS) were analyzed. External validation was performed using Kaplan-Meier Plotter and The Cancer Genome Atlas (TCGA) cohorts.</p><p><strong>Results: </strong><i>FTCD</i> knockdown significantly suppressed proliferation, invasion, and migration in CaR-1 and COL-3-JCK cells and reduced tumor growth <i>in vivo. FTCD</i> expression positively correlated with multiple EMT-related genes, particularly <i>COL1A2, SPARC, FZD7</i>, and <i>BMP7</i>. High <i>FTCD</i> expression was significantly associated with deeper tumor invasion and left-sided tumors. Patients with high <i>FTCD</i> expression showed significantly worse DFS [hazard ratio (HR)=2.00, <i>p</i>=0.012] and OS (HR=2.96, <i>p</i>=0.009). In multivariate analysis, high <i>FTCD</i> expression remained an independent prognostic factor for OS (HR=2.47, <i>p</i>=0.030), but not for DFS. Peritoneal and bone recurrences were more frequent in the high <i>FTCD</i> group. External validation cohorts showed similar prognostic trends.</p><p><strong>Conclusion: </strong><i>FTCD</i> may serve as a useful prognostic biomarker associated with aggressive tumor behavior and poor survival outcomes and may be a potential therapeutic target requiring further validation in CRC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"686-700"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350865","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":"Integrative Genomic and Clinical Profiling of Colorectal Cancer Liver Metastases to Guide Personalized Surgery and Liver Transplantation.","authors":"Dimitrios Moris, Brian Nguyen, Alexander Kroemer, Ioannis A Ziogas, Anastasios D Giannou, Thomas M Fishbein, Yuri S Genyk, Piyush Gupta","doi":"10.21873/cgp.20592","DOIUrl":"10.21873/cgp.20592","url":null,"abstract":"<p><strong>Background/aim: </strong>Colorectal cancer liver metastases (CRLM) remain a leading cause of cancer-related mortality. Although hepatic resection is the only established curative option, recurrence exceeds 60%, underscoring substantial biologic heterogeneity. Liver transplantation (LT) has re-emerged for highly selected patients with unresectable CRLM, but optimal biologic selection criteria remain undefined. This study integrates genomic and clinical data to develop a biologically grounded framework for surgical and transplant decision-making.</p><p><strong>Materials and methods: </strong>The Memorial Sloan Kettering 2017 metastatic colorectal cancer cohort was analyzed using cBioPortal-formatted clinical, genomic, and survival data. The study included patients with liver-only metastatic presentation. Genomic variables comprised <i>KRAS, NRAS, BRAF, TP53, APC, PIK3CA, SMAD4</i> alterations, tumor mutational burden, microsatellite instability, and copy-number alteration burden. Survival was assessed using Kaplan-Meier and Cox models. A predefined molecular-risk classification stratified patients into low (RAS/RAF wild-type, <i>SMAD4</i>-intact), intermediate (isolated <i>KRAS</i> mutation), and high risk (<i>NRAS, BRAF</i>, or <i>SMAD4</i> alterations). Machine-learning models predicted 24-month mortality.</p><p><strong>Results: </strong>Among 503 patients, molecular-risk groups demonstrated distinct survival (5-year OS: 74.5%, 56.6%, and 49.8%; <i>p</i><0.001). Intermediate- and high-risk groups were independently associated with worse survival (HR=1.71 and 2.60, respectively). Integrated clinicogenomic models modestly improved predictive performance (AUROC 0.697), with <i>BRAF</i> mutation, tumor sidedness, and age as key contributors. Inclusion of metastasectomy status increased AUROC but reflected post-treatment bias.</p><p><strong>Conclusion: </strong>Molecular-risk stratification and integrated modeling identify clinically meaningful prognostic groups in CRLM. These findings support incorporation of genomic profiling into precision surgical and transplant evaluation, while emphasizing the need for prospective validation.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"617-628"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350910","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}