Unveiling the hub genes in the SIGLECs family in colon adenocarcinoma with machine learning DOI Creative Commons
Tiantian Li,

Ji Yao

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

Published: April 8, 2024

Background Despite the recognized roles of Sialic acid-binding Ig-like lectins (SIGLECs) in endocytosis and immune regulation across cancers, their molecular intricacies colon adenocarcinoma (COAD) are underexplored. Meanwhile, complicated interactions between different SIGLECs also crucial but open questions. Methods We investigate correlation various properties, including cancer status, prognosis, clinical features, functional enrichment, cell abundances, checkpoints, pathways, etc. To fully understand behavior multiple SIGLECs’ co-evolution subtract its leading effect, we additionally apply three unsupervised machine learning algorithms, namely, Principal Component Analysis (PCA), Self-Organizing Maps (SOM), K-means, two supervised Least Absolute Shrinkage Selection Operator (LASSO) neural network (NN). Results find significantly lower expression levels COAD samples, together with a systematic enhancement correlations distinct SIGLECs. demonstrate SIGLEC14 affects Overall Survival (OS) according to Hazzard ratio, while using PCA further enhances sensitivity both OS Disease Free Interval (DFI). any single SIGLEC is uncorrelated stages, which can be improved by PCA. identify SIGLEC-1,15 CD22 as hub genes through Differentially Expressed Genes (DEGs), consistent our PCA-identified key components PC-1,2,5 considering status abundance. As an extension, use SOM for visualization show similarities differences patients. help us define subsamples corresponding changes cells T-stage, instance. Conclusion conclude most promising family treating COAD. offers significant prognosis analyses, unveils transition phases or potential subtypes

Language: Английский

Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer DOI Open Access

Andreea-Raluca Cozac-Szőke,

Dan Alexandru Cozac, Anca Negovan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1156 - 1156

Published: Jan. 29, 2025

Gastric cancer (GC) ranks as the fifth most prevalent malignant neoplasm globally, with an increased death rate despite recent advancements in research and therapeutic options. Different molecular subtypes of GC have distinct interactions immune system, impacting tumor microenvironment (TME), prognosis, reaction to immunotherapy. Tumor-infiltrating lymphocytes (TILs) TME are crucial for preventing growth metastasis, evidenced by showing that patients who a significant density TILs better survival rates. But cells evolved variety mechanisms evade surveillance, both sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) Programmed Death-Ligand 1 (PD-L1) playing pivotal role development immunosuppressive TME. They prevent T cell activation proliferation resulting decrease system’s capacity recognize eliminate cells. These checkpoint molecules function via different but complementary mechanisms, expression Siglec-15 being mutually exclusive PD-L1 and, therefore, providing approach. The review explores how affect patient outcomes GC, particular emphasis on their within potential targeting pathways

Language: Английский

Citations

1
Designing molecular hybrids as novel breast cancer therapeutics DOI Creative Commons

Devendra Singh Negi,

Irshad Ahmad,

Noora Ali Nasar

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: March 18, 2025

Language: Английский

Citations

0
MiRNA expression profiling and clinical implications in prostate cancer across various stages DOI Creative Commons

Zhengjie Xiang,

Tao Lin,

Jian Ling

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 5, 2025

This study aims to screen and identify microRNA (miRNA) expression profiles across different stages of prostate cancer (PCa) benign prostatic hyperplasia (BPH) using high-throughput sequencing. The seeks determine whether specific miRNAs show consistent differential various PCa, with the goal identifying potential biomarkers relevant disease progression. In this study, a total 12 specimens PCa BPH were collected from September 2021 June 2022 in Second Affiliated Hospital Nanchang University, 330,006, P.R. China (including 3 early localized tumor, local invasion, distant metastasis tumor BPH). profile miRNA was screened by sequencing technology, differentially expressed between each group bioinformatics analysis. Further targeted site analysis GO enrichment KEGG miRNA-derived genes performed on above miRNAs. Finally, hsa-miR-6715b-3p tissues verified qRT-PCR assay. A 1526 identified through By comparing groups, 228 identified, 100 upregulated 128 downregulated. Additionally, 69 novel predicted. results showed that highly compared tissues. presents preliminary investigation identifies as promising biomarker for Our findings validate high highlight its role critical oncogenic pathways. These provide theoretical foundation further functional studies explore clinical utility therapy resistance progression, contributing growing knowledge miRNA-based PCa.

Language: Английский

Citations

0
Potential of covalently linked tamoxifen hybrids for cancer treatment: recent update DOI

Devendra Singh Negi,

Irshad Ahmad, Donna J. Nelson

et al.

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(6), P. 1877 - 1898

Published: Jan. 1, 2024

This review highlights the potential of covalently linked tamoxifen hybrids as anti-cancer agents and provides valuable insights into their current progress.

Language: Английский

Citations

2
MicroRNA-Dependent Mechanisms Underlying the Function of a β-Amino Carbonyl Compound in Glioblastoma Cells DOI Creative Commons
Denis Mustafov, Shoib Sarwar Siddiqui, Andreas Kukol

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(29), P. 31789 - 31802

Published: July 15, 2024

Glioblastoma (GB) is an aggressive brain malignancy characterized by its invasive nature. Current treatment has limited effectiveness, resulting in poor patients' prognoses. β-Amino carbonyl (β-AC) compounds have gained attention due to their potential anticancerous properties.

Language: Английский

Citations

2
A Novel Electrochemiluminescence (ECL) Immunoassay for the Quantitation of Monoclonal Antibody (mAb) PYX-106 in Human Serum DOI

Feng Yin,

Diana Adhikari,

Xiaodong Liu

et al.

Current Analytical Chemistry, Journal Year: 2024, Volume and Issue: 20(6), P. 438 - 448

Published: March 28, 2024

Background:: PYX-106 is a novel monoclonal antibody (mAb), targeting the sialic acidbinding immunoglobulin-like lectin 15 (Siglec-15) in Tumor Microenvironment (TME). Precise measurement of essential for thorough assessment pharmacokinetics clinical investigations. Methods:: A Electrochemiluminescence (ECL) immunoassay quantitation PYX- 106 human serum was developed and validated. Biotinylated anti-PYX-106 Bio-A1A1 employed as capture antibody, ruthenylated Ru-A3G10 utilized detection ECL on Meso Scale Discovery (MSD) platform. Results:: This assay fully validated terms selectivity, accuracy, precision, hook effect, stability, etc., with dynamic range from 50.0 to 2,500 ng/mL under 2018 U.S. Food Drug Administration (FDA) guidance 2022 FDA ICH M10 guidance. Conclusion:: bioanalytical validation reported first time biological matrix, this has been successfully applied support trial PYX-106-101.

Language: Английский

Citations

1
MicroRNA:Siglec crosstalk in cancer progression DOI Creative Commons
Denis Mustafov, Maqsood Ahmad,

A. Serrano

et al.

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 81, P. 102502 - 102502

Published: July 18, 2024

Aberrant Siglec expression in the tumour microenvironment has been implicated malignancies and can impact behaviour patient survival. Further to this, engagement with sialoglycans induces masked antigen recognition promotes immune evasion, highlighting deregulated function. This necessitates elucidation of their profiles progression. MicroRNAs (miRNAs) mediated targeting represents a novel approach further elucidate potential clinical relevance. Although miRNA activity remains limited, we highlight current literature detailing miRNA:Siglec interactions within landscape provide insights for possible diagnostic therapeutic strategies Siglec/sialic acid axis.

Language: Английский

Citations

1
Differential expression of ST6GALNAC1 and ST6GALNAC2 and their clinical relevance to colorectal cancer progression DOI Creative Commons

Mohammed Saqif Ahmad,

Maria Braoudaki, Shoib Sarwar Siddiqui

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0311212 - e0311212

Published: Sept. 30, 2024

Colorectal cancer (CRC) has become a significant global health concern and ranks among the leading causes of morbidity mortality worldwide. Due to its malignant nature, current immunotherapeutic treatments are used tackle this issue. However, not all patients respond positively treatment, thereby limiting clinical effectiveness requiring identification novel therapeutic targets optimise strategies. The putative ligand Siglec-15, Sialyl-Tn (STn), is associated with tumour progression synthesised by sialyltransferases ST6GALNAC1 ST6GALNAC2. deregulation both within literature remain limited, involvement microRNAs (miRNAs) in STn production require further elucidation. Here, we identified miRNAs involved regulation via computational approach analysis miRNA binding sites were determined. In silico tools predicted miR-21, miR-30e miR-26b regulate gene, which had shown upregulated expression cohort. Moreover, each displayed high affinity towards seed region . Additionally, enrichment outlined pathways several hallmarks, including epithelial mesenchymal transition (EMT) MYC progression. Furthermore, our findings demonstrated that profile was significantly downregulated CRC tumours, low correlated poor survival outcomes when compared patient data. comparison counterpart, there no differences ST6GALNAC2 between normal tissues, evidenced immunohistochemistry analysis. Immunohistochemistry staining highlighted higher more prevalent human tissues regard conclusion, integrated reliant on deregulated sialyltransferase CRC, regulated oncomirs. We proposed other antigen Siglec-15/Sia axis.

Language: Английский

Citations

1
Impact of the Siglec-Sialoglycan Axis on the Cancer Immune Response DOI

Mohammed Saqif Ahmad,

Sara Seriah,

Shoib Sarwar Siddiqui

et al.

Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Sialic acid-binding immunoglobulin-like lectins (Siglecs) have heavily mediated the tumour landscape and shown significant deregulation in many malignancies by facilitating progression metastasis; such sialoglycan ligands also contributed to development. Primarily, Siglec/sialoglycan axis is capable of modulating immunosuppression signalling pathways, preventing myeloid cell activation subsequent generation an immune response. This book chapter highlights multifaceted roles outlines Siglec expression, their therapeutic potential as diagnostic prognostic biomarkers, current murine models techniques used further elucidate key pathways downstream targets. Additionally, we elaborated on role certain enzymes involved synthesis involvement glycosylation hypersialylation modulation microenvironment. Finally, suggest areas through which expand understanding function highlight maintaining heterogeneity. In addition this, usage Siglec-targeting therapies may enhance or optimise immunotherapeutic interventions upon experimental validation.

Language: Английский

Citations

0
Targeting Siglec-15 mediates mitochondrial retrograde regulation of cervical cancer development DOI
Jing Wang, Zenghui Li, Yifan He

et al.

Tissue and Cell, Journal Year: 2024, Volume and Issue: 93, P. 102713 - 102713

Published: Dec. 31, 2024

Language: Английский

Citations

0