Identification of anoikis-related molecular patterns and the novel risk model to predict prognosis, tumor microenvironment infiltration and immunotherapy response in bladder cancer DOI Creative Commons

Luochen Zhu,

Xiao Feng, Yi Hou

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 27, 2024

Background Anoikis, a unique form of cell death, serves as vital part the organism's defense by preventing shedding cells from re-attaching to incorrect positions, and plays pivotal role in cancer metastasis. Nonetheless, specific mechanisms among anoikis, clinical prognosis tumor microenvironment (TME) bladder (BLCA) are insufficiently understood. Method BLCA patients were classified into different anoikis subtypes based on expression candidate anoikis-related genes (ARGs), differences clinicopathological features, TME, immune infiltration, checkpoints between two analyzed. Next, TCGA cohort randomized train test groups 1:1 ratio. Subsequently, model was constructed predict via utilizing univariate Cox, LASSO multivariate Cox analyses, validated internally externally. Moreover, relationships risk score clinicopathologic immunotherapy response, antitumor drug sensitivity also In addition, representative evaluated using immunohistochemistry specimens, lines, functional experiments performed determine biological behavior hub gene PLOD1. Result Two definite subgroups identified. Compared ARGcluster A, assigned B characterized an immunosuppressive worse prognosis. Then, model, including PLOD1, EHBP1, CSPG4, constructed, low-risk group better accurate nomogram built improve applicability combining age, stage Score. infiltration features differed significantly high- groups. We found that exhibited lower dysfunction exclusion score, higher immunophenoscore (IPS), had more immunotherapy. Eventually, levels three verified our experiment, knockdown PLOD1 could inhibit invasion migration abilities lines. Conclusion These results demonstrated new direction precision therapy for BLCA, indicated ARGs might be helpful predicting therapeutic targets BLCA.

Language: Английский

Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy DOI Creative Commons
Yaxuan Wang, Li Ma, Jiaxin He

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 29, 2024

Background Cancer stem cells (CSCs) are a subset of within tumors that possess the unique ability to self-renew and give rise diverse tumor cells. These crucial in driving metastasis, recurrence, resistance treatment. The objective this study was pinpoint essential regulatory genes associated with CSCs prostate adenocarcinoma (PRAD) assess their potential significance diagnosis, prognosis, immunotherapy patients PRAD. Method utilized single-cell analysis techniques identify cell-related evaluate relation patient prognosis PRAD through cluster analysis. By utilizing datasets employing various machine learning methods for clustering, diagnostic models were developed validated. random forest algorithm pinpointed HSPE1 as most prognostic gene among genes. Furthermore, delved into association between immune infiltration, employed molecular docking investigate relationship its compounds. Immunofluorescence staining 60 tissue samples confirmed expression correlation Result This identified 15 analysis, highlighting importance diagnosing, prognosticating, potentially treating patients. specifically linked response immunotherapy, experimental data supporting upregulation poorer prognosis. Conclusion Overall, our findings underscore significant role unveil novel target related cell.

Language: Английский

Citations

24
Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target DOI Creative Commons
Yaxuan Wang, Jinfeng Wang, Lu Zhang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7), P. 1 - 20

Published: March 20, 2024

Abstract YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, biological functions bladder cancer remains be proven. We analysed variations YARS1 expression survival using multiple data sets, including TCGA‐BLCA, GSE13507 cancer‐specific tissue microarrays. Furthermore, we explored transcriptome data. Our findings revealed noteworthy correlation between immune infiltration cancer, as determined XCELL algorithm single‐cell analysis. In addition, employed TIDE evaluate responsiveness different cohorts checkpoint therapy. investigated regulatory associations various aspects senescence, ferroptosis stemness. Finally, established ceRNA network that directly linked overall prognosis, can serve prognostic biomarker cancer; interaction with MYC has implications cell Moreover, identified potential therapeutic target cancer.

Language: Английский

Citations

18
Long non‐coding RNA LINC01224 plays an oncogenic role in endometrial cancer via miR‐4673/TPX2 axis and activating Wnt/β‐catenin signaling pathway DOI Open Access

Shuqing Lv,

Xinlu Zhang, Fangfang Lang

et al.

BioFactors, Journal Year: 2025, Volume and Issue: 51(1)

Published: Jan. 1, 2025

Abstract Endometrial cancer (EC) is a prevalent gynecological malignancy with rising incidence and poor prognosis in advanced cases. Long non‐coding RNAs (lncRNAs) have been implicated various cancers, including EC. This study explores the role of lncRNA Linc01224 Analyzing TCGA data, we found expression significantly elevated EC tissues, correlating prognosis. Clinical samples validated these findings, showing higher levels tumor tissues. Knockdown cell lines (Hec‐1‐B Ishikawa) inhibited proliferation, migration, promoted apoptosis, alongside increased Bax decreased BCL2 expression. Furthermore, knockdown notably reduced Wnt2/β‐catenin pathway activation. We identified TPX2 as target miR‐4673, which regulated by through competing endogenous RNA (ceRNA) mechanism. Dual‐luciferase reporter assays confirmed miR‐4673 binding to TPX2. Rescue experiments revealed that reversed Linc01224‐induced proliferation highlighting TPX2's pivotal Linc01224's oncogenic function. In vivo, impeded growth metastasis xenograft model, c‐Myc, Cyclin D1, β‐catenin. These findings reveal novel ceRNA regulatory axis involving Linc01224, TPX2, elucidating progression pathway. emerges potential biomarker therapeutic for treatment.

Language: Английский

Citations

1
NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells DOI Creative Commons
Binghong Liu, Fei Song, Xiaoxia Zhou

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8), P. 1 - 11

Published: March 25, 2024

Abstract Dysregulated angiogenesis leads to neovascularization, which can promote or exacerbate various diseases. Previous studies have proved that NEDD4L plays an important role in hypertension and atherosclerosis. Hence, we hypothesized may be a critical regulator of endothelial cell (EC) function. This study aimed define the regulating EC elucidate their underlying mechanisms. Loss‐ gain‐of‐function detected mobility human umbilical vein cells (HUVECs) using Matrigel tube formation assay, proliferation migration. Pharmacological pathway inhibitors western blot were used determine mechanism NEDD4L‐regulated functions. Knockdown suppressed formation, migration HUVECs, whereas overexpression promoted these Moreover, progression are associated with phosphorylation Akt, Erk1/2 eNOS expression VEGFR2 cyclin D1 D3. Mechanically, further evidence was confirmed by Akt blocker MK‐2206, U0126 L‐NAME. Overexpression NEDD4L‐promoted angiogenesis, restrained inhibitors. In addition, cycle‐related proteins D3 also Our results demonstrated novel finding promotes Akt/Erk/eNOS pathways.

Language: Английский

Citations

6
Navigating the immune landscape with plasma cells: A pan‐cancer signature for precision immunotherapy DOI

Bicheng Ye,

Aimin Jiang, Liang Feng

et al.

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Immunotherapy has revolutionized cancer treatment; however, predicting patient response remains a significant challenge. Our study identified novel plasma cell signature, Plasma cell.Sig, through pan‐cancer single‐cell RNA sequencing analysis, which predicts outcomes to immunotherapy with remarkable accuracy. The signature was developed using rigorous machine learning algorithms and validated across multiple cohorts, demonstrating superior predictive power an area under the curve (AUC) exceeding 0.7. Notably, low‐risk group, as classified by exhibited enriched immune infiltration heightened tumor immunogenicity, indicating enhanced responsiveness immunotherapy. Conversely, high‐risk group showed reduced activity potential mechanisms of evasion. These findings not only enhance understanding intrinsic extrinsic landscapes within microenvironment but also pave way for more precise, biomarker‐guided approaches in oncology.

Language: Английский

Citations

5
The role of endothelial cell-related gene COL1A1 in prostate cancer diagnosis and immunotherapy: insights from machine learning and single-cell analysis DOI Creative Commons

Gu-Jun Cong,

Jingjing Shao,

Feng Xiao

et al.

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 8, 2025

Endothelial cells are integral components of the tumor microenvironment and play a multifaceted role in immunotherapy. Targeting endothelial related signaling pathways can improve effectiveness immunotherapy by normalizing blood vessels promoting immune cell infiltration. However, to date, there have been no comprehensive studies analyzing diagnosis treatment prostate adenocarcinoma (PRAD). By integrating clinical transcriptomic data from TCGA-PRAD, we initially identified key cell-related genes PRAD samples through single-cell analysis. Subsequently, cluster analysis was employed classify based on expression these genes, allowing us explore their correlation with patient prognosis outcomes. A diagnostic model then constructed validated using combination 108 machine learning algorithms. The XGBoost Random Forest algorithms highlighted significant COL1A1, further analyzed AR, EGFR multiplex immunofluorescence staining. In vitro experimental impact COL1A1 progression PRAD. Single-cell 12 differential prognostic associated cells. Cluster confirmed strong between both cancer responses. Diagnostic models developed various techniques demonstrated predictive capability cancer. Furthermore, patients' information, multiple analyses critical COL1A1. Immunofluorescence results that is highly expressed positively correlated AR EGFR. experiments confirm reducing levels inhibit progression. This study provides diagnosis, prognosis, findings, supported results, highlight as target for

Language: Английский

Citations

0
Machine learning model reveals the role of angiogenesis and EMT genes in glioma patient prognosis and immunotherapy DOI Creative Commons

Suyin Feng,

Long Zhu, Yan Qin

et al.

Biology Direct, Journal Year: 2024, Volume and Issue: 19(1)

Published: Nov. 12, 2024

Gliomas represent a highly aggressive class of tumors located in the brain. Despite availability multiple treatment modalities, prognosis for patients diagnosed with glioma remains unfavorable. Therefore, further exploration new biomarkers is crucial to enhance prognostic assessment and investigate more effective options. In this research, we utilized machine learning techniques assess significance genes related angiogenesis epithelial-mesenchymal transition (EMT) context patients. The random forest algorithm highlighted CALU, analysis indicated that effect CALU on progression may be regulated by MYC. Different approaches were employed our investigation uncover associated EMT glioma. Our findings verify connection between these glioma, as well results immunotherapeutic interventions. Notably, through experimental verification, identified marker inhibiting expression can impede

Language: Английский

Citations

2
Comprehensive analysis of the value of angiogenesis and stemness‐related genes in the prognosis and immunotherapy of ovarian cancer DOI Creative Commons
Linsen Zhou, Yu Min, Qiqi Cao

et al.

BioFactors, Journal Year: 2024, Volume and Issue: 51(1)

Published: Dec. 20, 2024

Abstract Tumor angiogenesis and the presence of cancer stem cells (CSCs) are critical characteristics tumors. Previous research has demonstrated that promote tumor angiogenesis, while increased vascularity, in turn, fosters growth cells. This creates a detrimental cycle contributes to progression. However, studies investigating stemness ovarian (OV) limited. In this study, we employed cluster analysis LASSO methods assess significance angiogenesis‐ stemness‐related genes efficacy OV immunotherapy. Through multivariate Cox regression Friends analysis, identified TNFSF11 as most significant prognostic gene associated with stemness. Additionally, molecular docking results confirmed exhibits high affinity for sorafenib sunitinib. summary, first time, conducted comprehensive roles prognosis immunotherapy patients, revealing novel therapeutic target.

Language: Английский

Citations

2
NSG2: a promising prognostic marker shaping the immune landscape of breast cancer DOI Creative Commons
Xuan Li,

Qihai Gu,

Ping‐Ping Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 18, 2024

Breast cancer (BC) remains a significant health issue globally and most common cause of mortality in women. Enhancing our understanding on biomarkers may greatly improve both diagnostic therapeutic approaches to this disease.

Language: Английский

Citations

1
N6-methyladenosine-modified SRD5A3, identified by IGF2BP3, sustains cisplatin resistance in bladder cancer DOI Creative Commons
Kai Liao, Jing Li,

Cai-Xian He

et al.

Human Cell, Journal Year: 2024, Volume and Issue: 38(1)

Published: Dec. 16, 2024

Resistance to cisplatin-based chemotherapy limits the clinical benefit some bladder cancer patients, and understanding epigenetic regulation mechanism of cisplatin (CDDP) resistance in from perspective N6-methyladenosine (m6A) modification may optimize CDDP-based treatments. The study identified SRD5A3 as an oncogene for stabilized by a m6A reader, IGF2BP3, sustain CDDP resistance. Our results revealed that expression was elevated human tissues cell lines, this elevation more evident CDDP-resistant T24 5637 cells. Results CCK-8 assay, colony formation EdU staining, flow cytometric analysis knockdown IGF2BP3 reduced proliferation prevented chemoresistance methylated RNA immunoprecipitation-PCR, immunoprecipitation luciferase reporter assay showed recognized its mRNA. Nude mice implanted subcutaneously with cells were injected intraperitoneally (2 mg/kg) every 3 days 35 demonstrated effectively inhibited tumor growth subcutaneous implantation model. Collectively, unveils IGF2BP3-mediated facilitates progression induces resistance, providing rational therapeutic targets patients.

Language: Английский

Citations

1