Discover. Oncology最新文献

{"title":"Circadian rhythms and cancer: implications for timing in therapy.","authors":"Mohamed El-Tanani, Syed Arman Rabbani, Areeg Anwer Ali, Ibrahim Ghaleb Ali Alfaouri, Hamdi Al Nsairat, Israa Hamid Al-Ani, Alaa A Aljabali, Manfredi Rizzo, Dimitrios Patoulias, Mohammad Ahmed Khan, Suhel Parvez, Yahia El-Tanani","doi":"10.1007/s12672-024-01643-4","DOIUrl":"https://doi.org/10.1007/s12672-024-01643-4","url":null,"abstract":"<p><p>Circadian rhythms, intrinsic cycles spanning approximately 24 h, regulate numerous physiological processes, including sleep-wake cycles, hormone release, and metabolism. These rhythms are orchestrated by the circadian clock, primarily located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Disruptions in circadian rhythms, whether due to genetic mutations, environmental factors, or lifestyle choices, can significantly impact health, contributing to disorders such as sleep disturbances, metabolic syndrome, and cardiovascular diseases. Additionally, there is a profound link between the disruption of circadian rhythms and development of various cancer, the influence on disease incidence and progression. This incurred regulation by circadian clock on pathways has its implication in tumorigenesis, such as cell cycle control, DNA damage response, apoptosis, and metabolism. Furthermore, the circadian timing system modulates the efficacy and toxicity of cancer treatments. In cancer treatment, the use of chronotherapy to optimize the timing of medical treatments, involves administering chemotherapy, radiation, or other therapeutic interventions at specific intervals to enhance efficacy and minimize side effects. This approach capitalizes on the circadian variations in cellular processes, including DNA repair, cell cycle progression, and drug metabolism. Preclinical and clinical studies have demonstrated that chronotherapy can significantly improve the therapeutic index of chemotherapeutic agents like cisplatin and 5-fluorouracil by enhancing anticancer activity and reducing toxicity. Further research is needed to elucidate the mechanisms underlying circadian regulation of cancer and to develop robust chronotherapeutic protocols tailored to individual patients' circadian profiles, potentially transforming cancer care into more effective and personalized treatment strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"767"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845837","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":"BUD23 promote the cell proliferation ability by affecting the PPAR signaling pathways: evidence from the online dataset and cell experiment.","authors":"Tao Huang, Binbin Jiao, Zhenkai Luo, Xiaolei Zhang, Zengjun Wang","doi":"10.1007/s12672-024-01648-z","DOIUrl":"10.1007/s12672-024-01648-z","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer is a major public health challenge for men worldwide, being the second most common cancer diagnosis and the fifth leading cause of cancer-related deaths among men. The etiology of prostate cancer is multifactorial, with age, genetic predispositions, and lifestyle factors playing critical roles. The role of the peroxisome proliferator-activated receptors (PPARs) in prostate cancer remains complex and not fully elucidated.</p><p><strong>Methods: </strong>Transcriptomic data from The Cancer Genome Atlas (TCGA) were utilized for this study. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Gene Set Enrichment Analysis (GSEA). A prognosis-prediction model was constructed using Cox regression and LASSO analysis. Functional experiments, including Western blotting, quantitative PCR (qPCR), Cell Counting Kit-8 (CCK-8) assays, and EdU incorporation assays, were performed to validate the role of BUD23 in prostate cancer.</p><p><strong>Results: </strong>Significant differences were observed in the immune microenvironment and HLA gene expression profiles between high and low PPAR expression groups in prostate cancer. The high PPAR group exhibited a less active immune microenvironment with higher fractions of immunosuppressive T regulatory cells (Tregs). A robust prognostic model identified key genes, including BUD23, associated with patient survival. Elevated BUD23 expression was correlated with more aggressive clinical features such as advanced pathological stages, nodal metastasis, and higher Gleason scores. Knockdown of BUD23 in PC-3 and LNCaP prostate cancer cell lines significantly inhibited cell proliferation. Western blotting and qPCR confirmed effective BUD23 knockdown, and CCK-8 and EdU assays demonstrated reduced cell proliferation. BUD23 knockdown resulted in significant reductions in PPAR-α, PPAR-β, and PPAR-γ protein levels, suggesting a regulatory axis between BUD23 and PPARs in prostate cancer.</p><p><strong>Conclusion: </strong>The study highlights the distinct roles of PPARα, PPARβ/δ, and PPARγ in prostate cancer progression and their potential as therapeutic targets. Elevated BUD23 expression is associated with aggressive prostate cancer features and patient survival, making it a potential prognostic biomarker. The knockdown of BUD23 not only inhibited cell proliferation but also reduced the expression of PPAR-related proteins, indicating a potential regulatory axis between BUD23 and PPARs. These findings suggest that targeting BUD23 could modulate PPAR signaling and inhibit tumor growth in prostate cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"750"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784540","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":"Computer-aided analysis reveals metallothionein-positive cancer-associated fibroblasts promote angiogenesis in gastric adenocarcinoma.","authors":"Xiaolong Jin, Yu Tian, Haoran Zhu, Yuewen Sun, Zhenxing Zhang","doi":"10.1007/s12672-024-01614-9","DOIUrl":"10.1007/s12672-024-01614-9","url":null,"abstract":"<p><p>Gastric adenocarcinoma (GC), along with its tumor microenvironment (TME), poses great challenges for clinical treatment strategies. Single-cell sequencing has become an important tool for analyzing TME heterogeneity, cell subpopulation, and gene expression patterns. 56 GC single-cell sequencing samples were analyzed, focusing on TME by delineating cancer cells, cancer-associated fibroblasts (CAFs), and macrophages. The spatial transcriptome was used to clarify the distribution characteristics of each cellular component in the tissue slice. Despite the widespread genetic mutations observed in cancer cells, certain recurrent alterations were identified in specific chromosomal regions. The heterogeneity among GC cells is profound, four cancer cell subpopulations were identified through drug sensitivity profiling. Subtype 4, although only present in some samples, demonstrates the strongest stemness and metabolic activity, possibly indicative of an early-stage cancer subpopulation. Their drug sensitivity profiles may hold promise for guiding clinical intervention. In addition, robust spatial co-localization patterns were observed between CAFs, M2 macrophages, and endothelial cells. CAFs were further categorized into six subgroups, among which a novel subgroup termed metallothionein(mt)-positive CAF (mtCAF), characterized by elevated expression of metallothionein 1X (MT1X) and subsequent vascular endothelial growth factor A (VEGFA) secretion, was identified. Immunohistochemistry preliminary confirmed the presence of this unique CAF subgroup. Additionally, M2d macrophages, besides exhibiting high VEGFA expression, also demonstrated various growth factors such as Aamphiregulin (AREG). The M2d-mtCAF axis may play an important role in GC angiogenesis. This study not only enhances our understanding of the TME heterogeneity in GC but also sheds light on the interaction between CAFs and tumor-associated macrophages (TAMs) in tumor angiogenesis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"751"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The T cell-mediated tumor killing patterns revealed tumor heterogeneous and proposed treatment recommendation in ovary cancer.","authors":"Xinglin Wen, Beining Yin, Li Lin, Long Liu, Siyuan Weng, Hui Xu, Yuyuan Zhang, Jinhai Deng, Ruiying Liao, Cungeng Fan","doi":"10.1007/s12672-024-01635-4","DOIUrl":"10.1007/s12672-024-01635-4","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, but the role of genes related to T cell-mediated tumor killing (TTK) sensitivity in ovarian cancer (OV) is unclear.</p><p><strong>Methods: </strong>This study analyzed 1367 OV patients and 11 independent cohorts. The unsupervised clustering was conducted to identify three tumor subtypes based on genes that regulate tumor cell sensitivity to TTK (GSTTKs). The biological characteristics, genetic variations, immunological landscape, and therapeutic evaluation for each subtype were further explored.</p><p><strong>Results: </strong>Patients were divided into three reproducible subtypes based on 61 GSTKKs associated with prognosis. C1 was likely to be an invasive subtype with the worst prognosis and highly unstable genome. C2 might be an immune-active subtype with the best prognosis, high immune infiltration and preferable response to immunotherapy. C3 might be a metabolic subtype, resistant to immunotherapy, but sensitive to drug therapy. Following an extensive exploration into a variety of distinct molecular features between the three subtypes, the results suggested that C2 patients were considered to derive significant efficacy from immunotherapy. For C1 and C3 patients, chemotherapy might be an ideal treatment strategy.</p><p><strong>Conclusions: </strong>In this study, three GSTKKs-based subtypes were identified by assessing TTK patterns in OV. These new insights further improved our understanding of GSTTKs and might refine clinical treatment strategies for OV patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"753"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783701","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":"Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocellular carcinoma through stabilizing HNF4α protein.","authors":"Si-Han Wu, Meng-Chao Xiao, Fang Liu, Huan-Yu Hong, Chen-Hong Ding, Xin Zhang, Wei-Fen Xie","doi":"10.1007/s12672-024-01661-2","DOIUrl":"10.1007/s12672-024-01661-2","url":null,"abstract":"<p><strong>Objectives: </strong>Hepatocyte nuclear factor 4α (HNF4α) is a key regulator of hepatocyte function and has a strong therapeutic effect on hepatocellular carcinoma (HCC) by inducing the differentiation of hepatoma cell into hepatocytes. Our previous study showed that Tribbles homolog 3 (TRIB3) directly interacts with and promotes the degradation of HNF4α in non-alcoholic fatty liver disease (NAFLD). Disrupting the TRIB3-HNF4α interaction by a cell-permeating peptide, called P-T3H2, stabilized HNF4α protein. This study aimed to assess the anti-tumor impact of P-T3H2 in HCC.</p><p><strong>Methods: </strong>The expression of TRIB3 and HNF4α was evaluated using western blot and immunohistochemistry (IHC). Hepatic functions and cellular senescence of HCC cells were evaluated through periodic acid-Schiff (PAS) staining, acetylated low-density lipoprotein (ac-LDL) uptake and senescence-associated β-galactosidase (SA-β-gal) activity staining, respectively. RNA-Seq analysis was performed to identify differentially expressed genes in Huh7 cells treated with P-T3H2. The impact of P-T3H2 on HCC malignancy was assessed in vitro and in vivo.</p><p><strong>Results: </strong>TRIB3 exhibited a negative correlation with HNF4α in both human and mouse HCC tissues. The administration of P-T3H2 significantly inhibited the malignancy of HCC cells. Additionally, P-T3H2 stabilized HNF4α protein and facilitated the restoration of hepatic functions and the cellular senescence in HCC cells. RNA-Seq analysis demonstrated that P-T3H2 enhanced the transcriptional activity of HNF4α in HCC. Furthermore, P-T3H2 effectively suppressed the carcinogenesis and progression of HCC in mice.</p><p><strong>Conclusion: </strong>P-T3H2 suppressed HCC progression through the stabilization of HNF4α protein and may be a promising therapeutic candidate for clinical application in the treatment of HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"752"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of common core genes and pathways in childhood sepsis and cancer by bioinformatics analysis.","authors":"Yi-Ran He, Ni Ding, Ming-Chen Han, Hong-Yu He, Li-Zhen Xuan, Zhun-Yong Gu, Ming Zhong, Min-Jie Ju","doi":"10.1007/s12672-024-01651-4","DOIUrl":"10.1007/s12672-024-01651-4","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis and cancer are both leading causes of death worldwide, and they share several pathophysiological characteristics. Some studies have suggested a possible association between sepsis and cancer; however, few have investigated the core genes involved in both diseases.</p><p><strong>Methods: </strong>Core genes common to both sepsis and cancer were identified using pediatric sepsis datasets (GEO: GSE26378, GSE4607, GSE8121 and GSE13904) and cancer databases (TCGA: BRCA, COADREAD, ESCA, KIRC, LIHC, LUAD, STAD). Gene Ontology (GO) and Reactome enrichment analyses, along with a protein-protein interaction (PPI) network analysis, were performed. Pharmacophore screening was applied to predict the targets of oxymatrine and ulinastatin, and potential target genes shared by both cancer and sepsis were identified. Survival analysis was performed. The association between the target genes and tumor size and number of positive lymph nodes was investigated by Pearson correlation analysis. The association between the target genes and tumor stage was investigated by Fisher's exact test. Molecular docking analysis was performed to evaluate the affinity of the candidate drugs for their targets.</p><p><strong>Results: </strong>A total of 641 common genes were identified. GO enrichment analysis showed that common genes were enriched in neutrophil degranulation, inflammatory response and innate immune response. Reactome enrichment analysis showed that common genes were enriched in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, transcriptional regulation of granulopoiesis and interleukin-10 signaling. The PPI network showed that the top 10 core genes were TLR4, IL1B, IL10, ITGAM, TLR2, PTPRC, CDK1, FOS, MMP9 and ITGB2. The survival analysis showed that the high expression of BCAT1, CSAD, G6PD, GM2A, MMP9, PYGL and TOP2A was associated with poorer prognosis in several cancers. Molecular docking showed that oxymatrine and ulinastatin can bind to protein targets with highly stable binding.</p><p><strong>Conclusions: </strong>We identified genes with common effects on both childhood sepsis and cancer, which provides new insights into the association between sepsis and cancer. In addition, two drugs with potential clinical application value were identified. Further studies are required to validate the role of these common core genes in sepsis and cancer and to evaluate the potential utility of these drugs.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"749"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783698","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":"Unraveling molecular signatures and prognostic biomarkers in glioblastoma: a comprehensive study on treatment resistance and personalized strategies.","authors":"Jinmin Xue, Jie Zhang, Jing Zhu","doi":"10.1007/s12672-024-01649-y","DOIUrl":"10.1007/s12672-024-01649-y","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a highly aggressive primary brain tumor with limited treatment success and poor prognosis. Despite surgical resection and adjuvant therapies, GBM often recurs, and resistance to radiotherapy and temozolomide presents significant challenges. This study aimed to elucidate molecular signatures associated with treatment responses, identify potential biomarkers, and enhance personalized treatment strategies for GBM.</p><p><strong>Methods: </strong>We conducted a comprehensive analysis using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The GEO dataset (GSE206225) was used to identify differentially expressed genes (DEGs) between radiation-sensitive/resistant and temozolomide-sensitive/resistant GBM samples. TCGA data were utilized for subsequent analyses, including Lasso-Cox regression, risk score model construction, Kaplan-Meier survival analysis, and gene set enrichment analysis (GSEA). Hub genes were identified through survival analysis, and a gene prognostic nomogram was developed. Additionally, validation of the three-gene risk signature through multiple external cohorts and validation of protein expression levels were performed.</p><p><strong>Results: </strong>DEG analysis identified 111 genes associated with chemoradiotherapy resistance, providing insights into the complex landscape of GBM treatment response. The risk score model effectively stratified patients, showing significant differences in overall survival and progression-free survival. GSEA offered a deeper understanding of pathway activities, emphasizing the intricate molecular mechanisms involved. NNAT, IGFBP6, and CYGB were identified as hub genes, and a gene prognostic nomogram demonstrated predictive accuracy.</p><p><strong>Conclusion: </strong>This study sheds light on the molecular intricacies governing GBM treatment response. The identified hub genes and the gene prognostic nomogram offer valuable tools for predicting patient outcomes and guiding personalized treatment strategies. These findings contribute to advancing our understanding of GBM biology and may pave the way for improved clinical management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"743"},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766597","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":"CMTM6 status predicts survival in head and neck squamous cell carcinoma and correlates with PD-L1 expression.","authors":"Anne-Sophie Becker, Nicolas Wieder, Sarah Zonnur, Annette Zimpfer, Mareike Krause, Björn Schneider, Daniel Fabian Strüder, Ann-Sophie Burmeister, Andreas Erbersdobler, Christian Junghanss, Claudia Maletzki","doi":"10.1007/s12672-024-01554-4","DOIUrl":"10.1007/s12672-024-01554-4","url":null,"abstract":"<p><p>We retrospectively analyzed 129 treatment-naïve head and neck squamous cell carcinomas (HNSCCs) for the expression of programmed death ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs). We evaluated the relationships among these markers, human papilloma virus (HPV) status, and overall survival (OS). PD-L1 and CMTM6 (combined positive score (CPS) ≥ 1 and ≥ 5) were detected in ~ 70% of HNSCCs. HPV status had insignificant effects on marker expression. Most PD-L1-positive cases showed concomitant CMTM6 expression with comparable staining patterns. While PD-L1 and CMTM6 mRNA expression levels correlated with PD-L1 and CMTM6 protein status, no significant correlation was observed for PD-L1 and CMTM6 mRNA expression. Tumors expressing PD-L1 (p < 0.0001) and/or CMTM6 (p < 0.05) were associated with the best OS. A high density of TILs (p < 0.01), CD8⁺ T cells (p < 0.001), and CD68/CD163 ratio > 1 were prognostically relevant. In addition to HPV status, PD-L1 and CD8⁺ T cells, CMTM6 was identified as an independent prognostic factor using a multivariate Cox regression analysis. PD-L1 and CMTM6 correlated with TILs and CD8⁺ cells but not with HPV. Our results identified CMTM6 as an important interaction partner in the crosstalk between TILs, CD8⁺ T cells, and PD-L1, which mediates anticancer efficacy. Assessments of CMTM6 may be helpful for prognostic prediction, and it may serve as a reliable biomarker for immunotherapy selection.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"745"},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and construction of prognostic clusters and risk-prognosis model based on aging-immune related genes in bladder cancer.","authors":"Nihao Cao, Fei Cheng, Jincai Zhou, Ning Liu","doi":"10.1007/s12672-024-01655-0","DOIUrl":"10.1007/s12672-024-01655-0","url":null,"abstract":"<p><strong>Background: </strong>Faced with the current global ageing situation, advanced age has become a risk factor for bladder carcinogenesis progression and immunotherapy. Exploring the common mechanisms of aging and immune in bladder cancer and finding new prognostic markers and immunotherapeutic targets has become an urgent issue.</p><p><strong>Method: </strong>Aging-immune related genes (AIGs) were collected from the public databases MSIGDB, HAGR and ImmPort, and hub AIGs were finally identified in the TCGA-BLCA disease cohort by expression, prognosis, and clinicopathological correlation analysis, and the correlation of hub AIGs with immune microenvironment, immunotherapeutic response, ferroptosis and m6A methylation was verified. Subsequently, prognostic clusters and risk-prognosis models for AIGs was constructed by cluster analysis and multifactorial Cox regression analysis, and the gene mutation and immune infiltration characteristics of the different clusters were explored. Finally, the expression level of related genes was verified by immunohistochemical experiments using patient samples from our medical center.</p><p><strong>Result: </strong>145 potential prognostic AIGs were collected in bladder cancer and finally clarified NFKB1 and IL7 with significant expression differences, prognostic value and age correlation. By single gene analysis, hub AIGs were explored to be significantly correlated with immunotherapeutic response, immune microenvironment, ferroptosis and m6A methylation. Subsequently, the risk-prognosis model was constructed with Riskscore = (0.0581)*NFKB1 + (- 0.2285)*IL7. And prognostic clusters based on hub AIGs was performed by cluster analysis, which clarified that the high-risk group was the pro-cancer group, which had a lower mutation rate of hub genes and higher of neutrophil infiltration. Finally, immunohistochemistry of patients confirmed that IL7 and NFKB1 were underexpressed in bladder cancer, and the proliferation and migration ability of tumor cells were significantly decreased after overexpression of these genes.</p><p><strong>Conclusion: </strong>This study is the first to identify NFKB1 and IL7 as hub AIGs in bladder cancer, which provide new prognostic markers and immunotherapeutic targets.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"742"},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767271","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 value of preoperative D-dimer to albumin ratio in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy.","authors":"Zhen Pan, Ye Wang, Shoufeng Li, Huajun Cai, Guoxian Guan","doi":"10.1007/s12672-024-01542-8","DOIUrl":"10.1007/s12672-024-01542-8","url":null,"abstract":"<p><strong>Background: </strong>The prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain.</p><p><strong>Purpose: </strong>The objective of this study was to investigate the prognostic significance of the DAR in LARC.</p><p><strong>Methods: </strong>A total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed.</p><p><strong>Results: </strong>The study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697).</p><p><strong>Conclusion: </strong>The DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"746"},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767308","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}