Cancer Cell International最新文献

{"title":"PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial.","authors":"Peng Sun, Hong Cen, Haiyan Yang, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu, Zhi-Ming Li","doi":"10.1186/s12935-025-03669-2","DOIUrl":"https://doi.org/10.1186/s12935-025-03669-2","url":null,"abstract":"<p><strong>Background: </strong>This investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).</p><p><strong>Methods: </strong>This was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles. The primary efficacy endpoint was the objective response rate (ORR).</p><p><strong>Results: </strong>The ORR observed in the full study population was 53.8% (95% confidence interval [CI]: 37.2-69.9). The median duration of response was 5.7 months (95% CI: 4.3-9.1), and the median progression-free survival was 5.4 months (95% CI: 1.8-6.7). The 1-year OS rate was 65.5% (95% CI: 48.1-78.3). Frequently observed adverse events included decreases in neutrophil counts (74.4%), white blood cell counts (64.1%) and platelet counts (64.1%).</p><p><strong>Conclusions: </strong>This study highlights the potential of linperlisib plus GEMOX as a treatment for R/R DLBCL, demonstrating a tolerable safety profile and encouraging efficacy results.</p><p><strong>Trial registration: </strong>NCT04500561.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"39"},"PeriodicalIF":5.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do wolframin, P-glycoprotein, and GRP78/BiP cooperate to alter the response of L1210 cells to endoplasmic reticulum stress or drug sensitivity?","authors":"Simona Kurekova, Lucia Pavlikova, Mario Seres, Viera Bohacova, Jana Spaldova, Albert Breier, Zdena Sulova","doi":"10.1186/s12935-025-03661-w","DOIUrl":"https://doi.org/10.1186/s12935-025-03661-w","url":null,"abstract":"<p><p>In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP expression and modulation of the expression of several other proteins active in the cellular response to ERS (like CHOP, spliced XBP1, 50-kDa ATF6 protein fragment and others) in P-gp positive cells. Wolframin is an ER transmembrane protein, product of the WFS1 gene whose mutations are associated with Wolfram syndrome. However, this protein is frequently overexpressed in cells undergoing ERS and its expression may accompany changes in the above ERS markers. Therefore, our aim in this work was to investigate wolframin expression in P-gp-negative and P-gp-positive murine leukemia L1210 cells in relation to ERS related proteins in normal or ERS condition. We induced ERS in cells either by blocking N-glycosylation in the ER with tunicamycin or by blocking ER Ca²⁺-ATPase activity with thapsigargin, as known ER stressors. The results of this paper demonstrated increased wolframin expression in P-gp positive cells compared to P-gp negative cells. Immunoprecipitation experiments revealed the formation of complexes between wolframin and ERS related proteins (PERK, ATF6 and GRP78/BiP), the amount of which varied depending on the presence of the above ER stressors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"35"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of G2/M checkpoint classifier for personalized treatment in uterine corpus endometrial carcinoma.","authors":"Yiming Liu, Yusi Wang, Shu Tan, Xiaochen Shi, Jinglin Wen, Dejia Chen, Yue Zhao, Wenjing Pan, Zhaoyang Jia, Chunru Lu, Ge Lou","doi":"10.1186/s12935-025-03667-4","DOIUrl":"https://doi.org/10.1186/s12935-025-03667-4","url":null,"abstract":"<p><strong>Background: </strong>Uterine Corpus Endometrial Carcinoma (UCEC) is a highly heterogeneous tumor, and limitations in current diagnostic methods, along with treatment resistance in some patients, pose significant challenges for managing UCEC. The excessive activation of G2/M checkpoint genes is a crucial factor affecting malignancy prognosis and promoting treatment resistance.</p><p><strong>Methods: </strong>Gene expression profiles and clinical feature data mainly came from the TCGA-UCEC cohort. Unsupervised clustering was performed to construct G2/M checkpoint (G2MC) subtypes. The differences in biological and clinical features of different subtypes were compared through survival analysis, clinical characteristics, immune infiltration, tumor mutation burden, and drug sensitivity analysis. Ultimately, an artificial neural network (ANN) and machine learning were employed to develop the G2MC subtypes classifier.</p><p><strong>Results: </strong>We constructed a classifier based on the overall activity of the G2/M checkpoint signaling pathway to identify patients with different risks and treatment responses, and attempted to explore potential therapeutic targets. The results showed that two G2MC subtypes have completely different G2/M checkpoint-related gene expression profiles. Compared with the subtype C2, the subtype C1 exhibited higher G2MC scores and was associated with faster disease progression, higher clinical staging, poorer pathological types, and lower therapy responsiveness of cisplatin, radiotherapy and immunotherapy. Experiments targeting the feature gene KIF23 revealed its crucial role in reducing HEC-1A sensitivity to cisplatin and radiotherapy.</p><p><strong>Conclusion: </strong>In summary, our study developed a classifier for identifying G2MC subtypes, and this finding holds promise for advancing precision treatment strategies for UCEC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"34"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma.","authors":"Yuli Jian, Kangkang Yang, Jinjing Li, Ling Tang, Guang Zeng, Xiaoxin Sun, Xiao Yu, Abdullah Al-Danakh, Qiwei Chen, Deyong Yang, Shujing Wang","doi":"10.1186/s12935-025-03640-1","DOIUrl":"https://doi.org/10.1186/s12935-025-03640-1","url":null,"abstract":"<p><p>Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting immune microenvironment dynamics. In the study, through systematic bioinformatics analysis and experimental verification, we demonstrated that ST3Gal5 expression was elevated in tumor tissues of KIRC patients, correlating with poor prognosis, and ST3Gal1 was downregulated and associated with a better prognosis. Immunohistochemistry analysis confirmed the expression patterns of ST3Gal1 and ST3Gal5 in 30 KIRC patients. Furthermore, KIRC patients were stratified into two clusters based on ST3Gal1 and ST3Gal5 levels using consensus clustering to investigate their roles in KIRC tumorigenesis, immune characteristics and treatment sensitivity. KIRC patients in Cluster 2, characterized by increased ST3Gal5 and downregulated ST3Gal1 expression, exhibited increased expression of immune checkpoints, immune cell infiltration, immune escape scores, and worse prognosis. Knockdown of ST3Gal5 in KIRC cell lines (786-O and 769-P) resulted in reduced tumor proliferation, migration, and invasion in vivo and in vitro. Together, the dysregulation of sialyltransferases (ST3Gal1 and ST3Gal5) in KIRC influences tumorigenesis and immune responses. These findings underscore the potential of ST3Gal1 and ST3Gal5 as prognostic factors and immunotherapy targets for KIRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"36"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of metalloproteinase PAPPA accelerates cancer progression and correlates with immune cell infiltration in gastric cancer: insights from bioinformatics and in vitro investigations.","authors":"Shiya Yu, Shiyao Zheng, Jinwei Qiu, Hongming Lin, Xiaojuan Yu, Huiyan Chen, Junhong Wu, Weihang Wu, Jiong Chen, Yongyuan Chen, Jianwei Chen, Hu Zhao, Yu Wang","doi":"10.1186/s12935-025-03650-z","DOIUrl":"https://doi.org/10.1186/s12935-025-03650-z","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common malignant tumors in the digestive system. However, the development of its targeted therapies has been slow. Therefore, exploring the mechanisms of malignant behavior of GC is key to developing their treatment methods. Pregnancy-associated plasma protein-A(PAPPA) is thought to play an important role in the occurrence and progression of cancer, yet its significance in the development of GC has not been reported.</p><p><strong>Methods: </strong>Bioinformatics analysis elucidated PAPPA's expression in GC and its prognostic significance. The study correlated PAPPA expression with immune infiltration and signaling pathways. Cellular assays, including CCK-8, Western blotting, and flow cytometry, were utilized to examine PAPPA's role in gastric cancer cell apoptosis, migration, and invasion.</p><p><strong>Results: </strong>Bioinformatics analysis has demonstrated that the expression of PAPPA is upregulated in GC and correlates with poor prognosis. Correlation and Cox regression analyses have revealed that TNM staging, pathological staging, age, outcome assessment, postoperative tumor residue, and PAPPA expression are prognostic determinants in GC. Further analysis indicates that PAPPA is associated with the infiltration of various immune cells and pathways related to GC. Cellular experiments have shown that PAPPA promotes cell proliferation, and its deficiency can inhibit the proliferation of GC cells, inducing cell cycle arrest at the G1/S phase.</p><p><strong>Conclusions: </strong>The findings of this investigation suggest that PAPPA serves as a crucial modulator of GC, underscoring its potential as a GC treatment target.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"38"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TWIST1 regulates HK2 ubiquitination degradation to promote pancreatic cancer invasion and metastasis.","authors":"Xinxing Wang, Mingze Ma, Shuai Shao, Xianwen Xu, Chuan Qin, Ruxin Gao, Zhenhai Zhang","doi":"10.1186/s12935-024-03583-z","DOIUrl":"https://doi.org/10.1186/s12935-024-03583-z","url":null,"abstract":"<p><strong>Objective: </strong>TWIST1 is known to promote glycolysis and contribute to pancreatic cancer development; however, its underlying mechanisms remain poorly understood. This study aims to elucidate the molecular mechanisms by which TWIST1 influences aerobic glycolysis in pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>The expression levels of TWIST1, MMP9, MT1-MMP, and FDX1 in clinical tissues and cancer cell lines were assessed using quantitative reverse transcription PCR (QRT-PCR). Cell treatments with Elesclomol-Cu and 2-deoxyglucose (2DG) were conducted. Immunofluorescence staining and immunoprecipitation analyses were performed to investigate the binding relationship between TWIST1 and HK2. Colony formation and Transwell assays were utilized to evaluate the effects of TWIST1 on cell proliferation, migration, and invasion. Western blotting was employed to detect proteins related to cuproptosis and apoptosis, while ubiquitination assays assessed TWIST1's regulation of HK2 ubiquitination.</p><p><strong>Results: </strong>TWIST1 expression was significantly elevated in PDAC tissues, and over-expression of TWIST1 in PDAC cells enhanced colony formation and cell proliferation. Notably, HK2 levels were markedly higher in pancreatic cancer tissues compared to adjacent normal tissues. TWIST1 was found to directly bind and interact with HK2, showing co-localization in the cytoplasm of PDAC cells. Furthermore, TWIST1 was shown to stabilize HK2 by inhibiting its ubiquitin-mediated degradation. Knockdown of TWIST1 or HK2 enhanced the inhibitory effects of 2DG on cell migration and invasion. Treatment with Elesclomol-Cu and 2DG significantly reduced the expression of the cuproptosis-related factor FDX1 with no impact on other cell death factors.</p><p><strong>Conclusion: </strong>This study demonstrates that TWIST1 regulates the ubiquitination and degradation of HK2, thereby promoting glycolysis-induced cuproptosis and facilitating pancreatic cancer invasion and metastasis. Understanding the underlying mechanisms of PDAC, including the regulation of key proteins such as HK2 by TWIST1, is crucial for developing more effective treatment strategies. Findings highlight the importance of targeting these molecular pathways, which could lead to improved diagnostic and therapeutic approaches, ultimately enhancing patient outcomes and prognosis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"37"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular pathways in reproductive cancers: a focus on prostate and ovarian cancer.","authors":"Ayodeji Folorunsho Ajayi, Mega Obukohwo Oyovwi, Oyedayo Phillips Akano, Grace Bosede Akanbi, Florence Bukola Adisa","doi":"10.1186/s12935-025-03658-5","DOIUrl":"10.1186/s12935-025-03658-5","url":null,"abstract":"<p><p>Reproductive cancers, including prostate and ovarian cancer, are highly prevalent worldwide and pose significant health challenges. The molecular underpinnings of these cancers are complex and involve dysregulation of various cellular pathways. Understanding these pathways is crucial for developing effective therapeutic strategies. This review aims to provide an overview of the molecular pathways implicated in prostate and ovarian cancers, highlighting key genetic alterations, signaling cascades, and epigenetic modifications. A comprehensive literature search was conducted using databases such as PubMed, Web of Science, and Google Scholar. Articles focusing on molecular pathways in prostate and ovarian cancer were reviewed and analyzed. In prostate cancer, recurrent mutations in genes like AR, TP53, and PTEN drive tumor growth and progression. Androgen signaling plays a significant role, with alterations in the AR pathway contributing to resistance to antiandrogen therapies. In ovarian cancer, high-grade serous carcinomas are characterized by mutations in TP53, BRCA1/2, and homologous recombination repair genes. PI3K and MAPK pathways are frequently activated, promoting cell proliferation and survival. Epigenetic alterations, including DNA methylation and histone modifications, are also prevalent in both cancer types. The molecular pathways involved in prostate and ovarian cancer are diverse and complex. Targeting these pathways with precision medicine approaches holds promise for improving patient outcomes. Further research is needed to elucidate the mechanisms of resistance and identify novel therapeutic vulnerabilities.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"33"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EMT-driven plasticity prospectively increases cell-cell variability to promote therapeutic adaptation in breast cancer.","authors":"Lauriane Muller, Frédérique Fauvet, Christelle Chassot, Francesca Angileri, Angèle Coutant, Cyril Dégletagne, Laurie Tonon, Pierre Saintigny, Alain Puisieux, Anne-Pierre Morel, Maria Ouzounova, Pierre Martinez","doi":"10.1186/s12935-025-03637-w","DOIUrl":"10.1186/s12935-025-03637-w","url":null,"abstract":"<p><p>Cellular plasticity enables cancer cells to adapt non-genetically, thereby preventing therapeutic success. The epithelial-mesenchymal transition (EMT) is a type of plasticity linked to resistance and metastasis. However, its exact impact on population diversity and its dynamics under chemotherapy is unknown. We used single-cell transcriptomics to investigate phenotypic diversity dynamics upon treatment in two in vitro models of triple negative breast cancer (TNBC), where EMT-driven plasticity is either induced or spontaneously occurring. We report that EMT-driven plasticity confers higher phenotypic cell-cell variability (p < 0.001) while enriching for stem-like cells. Genetic and phenotypic cell-cell variability were not consistently correlated. High-plasticity populations displayed more pre-adapted cells before treatment (p = 0.03). In a population displaying spontaneous EMT and phenotypic variation, pre-adapted cells were a rare minority of high-scoring outliers whose expression patterns correlated with survival in TNBC patients subjected to chemotherapy (p = 0.03). Higher plasticity was not associated with a partial EMT status. Our results provide novel insights on how EMT-driven plasticity promotes a prospective diversification process increasing population phenotypic diversity, which can yield rare pre-adapted states before treatment. This highlights the need to tackle phenotypic diversity prior to treatment in high-plasticity tumours.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"32"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTMR6 downregulation contributes to cisplatin resistance in oral squamous cell carcinoma.","authors":"Kah Young Lee, Su Young Oh, Heon-Jin Lee, Tae-Geon Kwon, Jin-Wook Kim, Chang-Geol Shin, Su-Hyung Hong, So-Young Choi","doi":"10.1186/s12935-025-03654-9","DOIUrl":"10.1186/s12935-025-03654-9","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic effectiveness of cisplatin, a widely used chemotherapy drug for oral squamous cell carcinoma (OSCC), is often compromised by resistance, making it difficult to predict treatment outcomes. The role of myotubularin and myotubularin-related (MTMR) genes in cisplatin resistance remains unclear. We aimed to elucidate the molecular mechanisms underlying MTMR6 with cisplatin resistance in OSCC.</p><p><strong>Methods: </strong>MTMR6 expression was compared between UMSCC1 and cisplatin-resistant UM-Cis cells. Gain- and loss-of-function experiments involving MTMR6 was performed to evaluate its impact on cisplatin resistance. The regulatory role of hsa-miR-544a on MTMR6 expression was explored via antagomir and miRNA mimic assays. The relationship between MTMR6 protein levels and cisplatin sensitivity was assessed in OSCC patient tissues classified as sensitive or resistant to cisplatin monotherapy. A survival analysis based on The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) dataset was performed to evaluate the correlation between MTMR6 expression and patient outcomes following cisplatin treatment. In vivo cisplatin resistance was examined using mouse xenografts derived from MTMR6-knockdown UMSCC1 cells.</p><p><strong>Results: </strong>MTMR6 expression was markedly reduced in cisplatin-resistant UM-Cis cells compared to UMSCC1 cells. Functional analyses revealed that modulating MTMR6 activity alters cisplatin resistance. A luciferase assay confirmed that hsa-miR-544a regulates MTMR6 gene expression. Additionally, antagomir and miRNA mimics demonstrated that hsa-miR-544a enhances cisplatin resistance by suppressing MTMR6 expression. In OSCC patient tissues, higher MTMR6 protein levels were associated with cisplatin sensitivity, while cisplatin-resistant tissues had lower MTMR6 expression. Survival analysis of the TCGA HNSCC dataset indicated that low MTMR6 expression correlates with poorer outcomes in cisplatin-treated patients compared to those with high MTMR6 expression. Mouse xenografts derived from MTMR6-knockdown UMSCC1 cells exhibited increased resistance to cisplatin compared to controls.</p><p><strong>Conclusion: </strong>Assessing mRNA levels of MTMR6 and has-miR-544a in biopsy samples could help predict cisplatin responsiveness in OSCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"30"},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis.","authors":"Yuzhao Jin, Luyu Liao, Qianping Chen, Bufu Tang, Jin Jiang, Ji Zhu, Minghua Bai","doi":"10.1186/s12935-025-03643-y","DOIUrl":"10.1186/s12935-025-03643-y","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have found that neutrophil extracellular traps (NETs) are highly expressed in colorectal cancer (CRC) and are associated with poor prognosis. Currently, there are few studies on the relationship between NETs and CRC, so we tried to explore new markers based on NETs to assist in the treatment of CRC.</p><p><strong>Method: </strong>We jointly screened three major NETs genes through machine learning. Large-sample RNA transcriptome and single-cell transcriptome analysis further confirmed that TIMP1 is a core gene in NETs. We used small interfering RNA to knockdown TIMP1, and verified the ability of TIMP1 in CRC proliferation, invasion and migration through western blot, transwell, cell scratch assay, cell clone formation and other experiments.</p><p><strong>Result: </strong>We screened out three major NETs Genes: TIMP1, F3, and CRISPLD2 based on machine learning. The NETs score constructed based on this not only predicts the prognosis of CRC patients but also shows significant differences in MSI status, chenckpoints expression, and predicted efficacy of PD-L1 targeted therapy. Transcriptome and single-cell data reveal that TIMP1 is highly expressed in neutrophils and is associated with poor prognosis in colorectal cancer patients and the occurrence of ferroptosis. Biological experiments have proven that TIMP1 can promote the proliferation, invasion and migration of CRC.</p><p><strong>Conclude: </strong>Bioinformatics analysis combined with experimental verification showed that TIMP1 is related to ferroptosis and plays a promoting role in the invasion, migration and proliferation of CRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"31"},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}