CHI3L1: a key driver in gastritis-to-cancer transformation DOI Creative Commons
Tao Li, Huizhong Jiang, Yihong Gong

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 19, 2025

Abstract Background Gastric cancer, recognized as one of the most lethal malignancies globally, progresses through a complex, multi-stage development. Elucidating pathogenic mechanisms behind gastric carcinogenesis and identifying early diagnostic biomarkers are pivotal for decreasing prevalence cancer. Methods Using datasets on cancer its transformation from gastritis, we employed machine learning to create an model, key genes evaluating accuracy. We prioritized in gastritis-to-cancer progression, central driver gene. Pathway analysis revealed role. Tissue microarrays rat models validated networks, confirmed cell organoid models. also identified types secreting CHI3L1 using single-cell RNA sequencing multiplex immunohistochemistry, exploring their prognostic significance. Results 12 potentially involved transformation, with CHI3L1, MMP12, CXCL6, IDO1, CCL20 emerging top five via model. was pinpointed across spectrum, upregulation, along CD44, β-catenin, c-Myc, noted precancerous lesions. In vitro studies CHI3L1’s role activating CD44-β-catenin pathway induce malignancy. Furthermore, our findings indicate that fibroblasts dendritic cells principal sources secretion, factor is associated poor prognosis Conclusions This study highlights gene driving progression gastritis primarily by pathway, which enhances malignant traits. mainly secreted cells, high levels linked prognosis.

Language: Английский

Single‐cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target DOI Creative Commons
Jindong Xie, Anli Yang, Qianwen Liu

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(11)

Published: June 29, 2024

Abstract Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, development more efficacious strategies and exploration potential targets for metastatic cancer are urgently needed. The data six brain metastases (BCBrM) from two centres were collected, a comprehensive landscape entire tumour ecosystem was generated through utilisation single‐cell RNA sequencing. We utilised Monocle2 CellChat algorithms to investigate interrelationships among each subcluster. In addition, multiple signatures collected evaluate key components subclusters multi‐omics methodologies. Finally, we elucidated common expression programs malignant cells, experiments conducted vitro vivo determine functions interleukin enhancer‐binding factor 2 ( ILF2 ), which is gene module, BCBrM progression. found that major cell type exhibited diverse characteristics. Besides, our study indicated specifically associated BCBrM, experimental validations further demonstrated deficiency hindered Our offers novel perspectives on heterogeneity suggests could serve as promising biomarker or therapeutic target BCBrM.

Language: Английский

Citations

13
m6A modification of lncRNA ABHD11-AS1 promotes colorectal cancer progression and inhibits ferroptosis through TRIM21/IGF2BP2/ FOXM1 positive feedback loop DOI

Yibo Bian,

Shufen Xu,

Zhishuang Gao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 596, P. 217004 - 217004

Published: June 4, 2024

Language: Английский

Citations

10
Histone lactylation regulates PRKN-Mediated mitophagy to promote M2 Macrophage polarization in bladder cancer DOI
Xiaolin Deng,

Yuan Huang,

Jinge Zhang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114119 - 114119

Published: Jan. 23, 2025

Language: Английский

Citations

1
Loss of MNX1 Sensitizes Tumors to Cytotoxic T Cells by Degradation of PD‐L1 mRNA DOI Creative Commons
Zhengzheng Li, Lei Chen, Ge Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Immune checkpoint blockade (ICB) therapy, targeting programmed cell death ligand-1 (PD-L1)/programmed protein 1 (PD-1) axis and cytotoxic T-lymphocyte-associated 4 (CTLA-4), has exhibited amazing clinical outcomes in various types of cancers. However, only a small portion patients benefit from ICB indicating that the mechanism underlying immune is still unclear. Here, it reported motor neuron pancreas homeobox (MNX1), domain-containing transcription factor, contributes to tumor escape. MNX1 increases PD-L1 expression cancer cells by stabilizing mRNA rather than activating transcription. Mechanistically, exists cytoplasm interacts with Y-box binding (YBX1), multifunctional DNA/RNA-binding protein, enhance YBX1 mRNA. ablation activates T cell-mediated anti-tumor immunity sensitizes CTLA-4 therapy. Moreover, also facilitates progression an immune-independent manner cells. In addition, upregulated its adjacent long non-coding RNA MNX1-AS1 via HECT RLD domain containing E3 ubiquitin ligase 2 (HERC2). Together, these results reveal as novel regulator promising therapeutic potential.

Language: Английский

Citations

1
Exploring NUP62’s role in cancer progression, tumor immunity, and treatment response: insights from multi-omics analysis DOI Creative Commons
Lihong Chen, Youfu He,

Menghui Duan

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background NUP62, a key component of the nuclear pore complex, is closely associated with cellular functions and cancer progression. However, its expression patterns, prognostic value, relationship tumour immunity drug sensitivity across multiple cancers have not been systematically studied. This study used multi-omics analyses combined experimental validation in gastric to investigate expression, functional characteristics, clinical relevance NUP62 cancer. Methods Data from TCGA, GTEx, CPTAC databases were analyse mutation associations NUP62. Tools such as SangerBox, TIMER 2.0, GSEA employed evaluate between immune microenvironment, well involvement signalling pathways. Immunohistochemistry RT-PCR validate tissues. PRISM CTRP utilised assess correlation sensitivity. Results was significantly upregulated poor prognosis clear cell renal carcinoma (KIRC), lower-grade glioma (LGG), adrenocortical (ACC), while playing protective role others, bladder (BLCA) stomach (STAD). Functional showed that involved cycle regulation, DNA damage repair, immunity. High correlated increased infiltration cells, macrophages T higher response rate immunotherapy. Drug analysis identified marker various chemotherapeutic agents. Validation experiments demonstrated mRNA protein levels tissues than adjacent normal Conclusions plays critical shows potential biomarker for diagnosis, prognosis, therapeutic prediction. Its pathways highlights target immunotherapy precision medicine.

Language: Английский

Citations

1
Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer DOI Creative Commons
Jifeng Liu, Shurong Ma,

Dawei Deng

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 207 - 207

Published: March 18, 2025

Background: The reprogramming of lipid metabolism, especially glycerolipid metabolism (GLM), plays a key role in cancer progression and response to therapy. However, the molecular characterization GLM pancreatic (PC) remain unclear. Methods: A pan-cancer analysis metabolism-related genes (GMRGs) was first conducted assess copy-number variants, single-nucleotide variations, methylation, mRNA expression. Subsequently, PC characterized using lipidomics, single-cell RNA sequencing (scRNA-seq), spatial transcriptomic analysis. cluster based on bulk data from 930 samples identified GLM-associated subtypes, which were then analyzed for differences prognosis, biological function, immune microenvironment, drug sensitivity. To prioritize prognostically relevant GMRGs PC, we employed random forest (RF) algorithm rank their importance across samples. Finally, biomarker validated PCR immunohistochemistry. Results: Pan-cancer features cancers, while scRNA-seq, transcriptomics, lipidomics highlighted heterogeneity PC. Two subtypes with significant prognostic, biofunctional, microenvironmental, sensitivity ALDH2 as novel prognostic large number datasets clinical Conclusions: This study highlights crucial defines new subtype biomarker. These findings establish avenue studying prediction precision medicine patients.

Language: Английский

Citations

1
Deciphering cutaneous melanoma prognosis through LDL metabolism: Single‐cell transcriptomics analysis via 101 machine learning algorithms DOI
Jiaheng Xie, Dan Wu, Pengpeng Zhang

et al.

Experimental Dermatology, Journal Year: 2024, Volume and Issue: 33(4)

Published: April 1, 2024

Abstract Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic molecular contributors to cutaneous development, there remains critical knowledge gap concerning role lipids, notably low‐density lipoprotein (LDL), in this lethal skin cancer. This article endeavours bridge delving into intricate interplay between LDL metabolism melanoma, shedding light on how lipids influence tumour progression, immune responses potential therapeutic avenues. Genes associated with were extracted from GSEA database. We acquired analysed single‐cell sequencing data (GSE215120) bulk‐RNA data, including TCGA set, GSE19234, GSE22153 GSE65904. Our analysis unveiled heterogeneity across various cell types at level. Additionally, we constructed an LDL‐related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes highly correlated genes. The LRS serves as valuable tool assessing prognosis, immunity mutation status patients melanoma. Furthermore, conducted experiments A375 WM‐115 cells validate function PPP2R1A, pivotal gene LRS. comprehensive approach, combining advanced bioinformatics analyses review current literature, presents compelling evidence regarding significance microenvironment.

Language: Английский

Citations

5
Histone lactylation dynamics: Unlocking the triad of metabolism, epigenetics, and immune regulation in metastatic cascade of pancreatic cancer DOI Creative Commons
Xing Wang, Xiaohong Liu, Ruiling Xiao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217117 - 217117

Published: July 15, 2024

Cancer cells rewire metabolism to sculpt the immune tumor microenvironment (TME) and propel advancement, which intricately tied post-translational modifications. Histone lactylation has emerged as a novel player in modulating protein functions, whereas little is known about its pathological role pancreatic ductal adenocarcinoma (PDAC) progression. Employing multi-omics approach encompassing bulk single-cell RNA sequencing, metabolomics, ATAC-seq, CUT&Tag methodologies, we unveiled potential of histone prognostic prediction, patient stratification TME characterization. Notably, "LDHA-H4K12la-immuno-genes" axis introduced node into regulatory framework "metabolism-epigenetics-immunity," shedding new light on landscape PDAC Furthermore, heightened interplay between cancer counterparts via Nectin-2 liver metastasis with elevated HLS unraveled positive feedback loop driving evasion. Simultaneously, exhibited altered autonomous functionality across metastatic cascade. Consequently, exploration innovative combination strategies targeting metabolism-epigenetics-immunity holds promise curbing distant improving survival prospects for individuals grappling challenges PDAC.

Language: Английский

Citations

5
Targeting m7G-enriched circKDM1A prevents colorectal cancer progression DOI Creative Commons
Zhenqiang Sun, Yanxin Xu,

Chaohua Si

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Plenty of circRNAs have been reported to play an important role in colorectal cancer (CRC), while the reason abnormal circRNA expression still keep elusive. Here, we found that m7G RNA modifications were enriched some circRNAs, these catalyzed by METTL1, and GG motif was main site preference for circRNAs. We further confirmed METTL1 played a cancer-promoting CRC. then screened highly expressed circRNA, called circKDM1A, prevented degradation circKDM1A modification. CircKDM1A verified promote proliferation, invasion migration CRC vivo vitro. Its ability weakened after mutation. activate AKT pathway upregulating PDK1, consequently promoting progression. These results suggest m7G-modified promotes progression via activating pathway. Our study uncovers essential physiological function mechanism METTL1-mediated modification regulation stability

Language: Английский

Citations

5
GLIPR2: a potential biomarker and therapeutic target unveiled – Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma DOI Creative Commons

Wei Lin,

Siming Zhang, Chunyan Gu

et al.

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

Published: Feb. 26, 2024

Background Glioma pathogenesis related-2 (GLIPR2), an emerging Golgi membrane protein implicated in autophagy, has received limited attention current scholarly discourse. Methods Leveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS cBioPortal databases, scrutinized mutation patterns methylation landscapes. integration of bulk single-cell RNA sequencing facilitated elucidation relationships among cellular heterogeneity, immune infiltration, levels pan-cancer. Employing ROC KM analyses, unveiled the diagnostic prognostic potential cancers. Immunohistochemistry provided insights multicenter cohort spanning various cancer types. In vitro functional experiments, transwell assays, wound healing drug sensitivity testing, were employed to delineate tumor suppressive role GLIPR2. Results was significantly reduced neoplastic tissues compared its prevalence healthy tissues. Copy number variations (CNV) alterations exhibited discernible correlations with within Moreover, demonstrated implications, showing pronounced associations profiles numerous checkpoint genes relative abundance cells microenvironment. This multifaceted influence evident types, lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients LUAD significant decrease practical clinical settings. Elevated correlated improved outcomes specifically LUAD. Following radiotherapy, cases displayed increased presence + infiltrating constituents, indicating notable correlation heightened radiation-induced therapeutic modalities. A battery experiments validated suppressing malignant phenotype enhancing treatment sensitivity. Conclusion pan-cancer, LUAD, emerges as promising novel biomarker suppressor. Its involvement cell infiltration suggests immunotherapeutic target.

Language: Английский

Citations

4