M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single‐cell and bulk RNA‐Seq analysis

Qian, Weiwei; Wang, Qi; Zhang, Chi; Zhu, Jing; Zhang, Qing; Luo, Chun

doi:10.1002/jgm.3523

Cited by 3 publications

(3 citation statements)

References 54 publications

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“…SPOCD1 has also been linked to DNA methylation, which has been shown to be altered in AD[52,53]. Lastly, CHI3L2 has been suggested as potential biomarker in glioma[54], a condition which frequency varies between Hispanics and NHW[55,56].…”

Section: Discussionmentioning

confidence: 99%

MU-BRAIN: MUltiethnic Brain Rna-seq for Alzheimer INitiative

Yang,

Cieza,

Reyes-Dumeyer

et al. 2024

Preprint

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BackgroundsAlzheimer’s Disease (AD) exhibits a complex molecular and phenotypic profile. Investigating gene expression plays a crucial role in unraveling the disease’s etiology and progression. Transcriptome data across ethnic groups lack, negatively impacting equity in intervention and research.MethodsWe employed 565 brains across six U.S. brain banks (N=399 non-Hispanic Whites, N=113 Hispanics, N=12 African Americans) to generated bulk RNA sequencing from prefrontal cortex. We sought to identify cross-ancestry and ancestry-specific differentially expressed genes (DEG) across Braak stages, adjusting for sex, age at death, and RNA quality metrics. We further validated our findings using the Religious Orders Study/Memory Aging Project brains (ROS/MAP; N=1,095). We conducted Gene Set and Variation and Enrichment analysis (GSVA; GSEA). We employed a machine-learning approach for phenotype prediction and gene prioritization to construct a polytranscriptomics risk score (PTRS) splitting our sample into training and testing sub-samples, either randomly or by ethnicity (“ancestry-agnostic” and “ancestry-aware”, respectively). Lastly, we validated top DEG using single-nucleus RNA sequencing (snRNAseq) data.ResultsWe identified DEG associated with Braak staging: AD-known genesVGF(padj=3.78E-07) andADAMTS2(padj=1.21E-04) were consistently differentially expressed across statistical models, ethnicities, and replicated in ROS/MAP. Genes from the heat shock protein (HSP) family, e.g.HSPB7(padj=3.78E-07), were the top differentially expressed genes and replicated in ROS/MAP. Ethnic-stratified analyses prioritizedTNFSF14andSPOCD1as top Hispanics DEG. GSEA highlighted “Alzheimer disease” (padj=4.24E-06) and “TYROBP causal network in microglia” (padj=1.68E-08) pathways. Up- and down-regulated genes were enriched in several pathways (e.g. “Immune response activation signal pathways”, “Vesicle-mediated transport in synapse”, “cognition”). Ancestry-agnostic and ancestry-aware PTRS effectively classified brains (AUC=0.77 and 0.73 respectively) and replicated in ROS/MAP. snRNAseq validated prioritized genes, includingVGF (downregulated in neurons; padj=1.1 E-07).ConclusionsThis is the largest diverse transcriptome for AD in post-mortem tissue to our knowledge. We identified perturbated genes, pathways and network expressions in AD brains resulting in cross-ethnic and ethnic-specific findings, ultimately highlighting the diversity within AD pathogenesis. The latter underscores the need for an integrative and personalized approach in AD studies.

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Section: Discussionmentioning

confidence: 99%

MU-BRAIN: MUltiethnic Brain Rna-seq for Alzheimer INitiative

Yang,

Cieza,

Reyes-Dumeyer

et al. 2024

Preprint

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“…Over expression was involved in different pathologies: osteoarthritis [17], amyotrophic lateral sclerosis [18], multiple sclerosis and cancers [19,20]. Prognostic significance has been noted for renal cancer [21] and glioma [22,23]. A recent study by Ling Xue et al proposed a prognostic role in gastric adenocarcinoma [24].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study by Ling Xue et al proposed a prognostic role in gastric adenocarcinoma [24]. CHI3L2 is mainly secreted by tumor-associated macrophages and associated with metastasis progression and poor outcome [23,24]. The second gene, MGAT5, expresses a glycosyltransferase family member catalyzed by an essential step in the biosynthesis of branched, complex-type N-glycans (oligosaccharides).…”

Section: Discussionmentioning

confidence: 99%

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women

Skvortsova,

Abdikerim,

Yergali

et al. 2024

Genes

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Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10−6) and MGAT5 gene (p = 8.4 × 10−6). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10−4). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.

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Glioblastoma: A molecular insight into current discoveries and treatment directions

Świątek,

Kłodziński,

Ciesielski

et al. 2024

Medical Journal of Cell Biology

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Glioblastoma is a highly aggressive and complex pathology that has garnered significant interest among researchers and clinicians due to its high mortality rates. This research article provides a systematic analysis of key aspects related to glioblastoma, offering comprehensive insights into its underlying complexities. The text explores the epidemiological patterns, etiological factors, and genetic and molecular foundations underlying the development of GBM. It also examines the interplay between the immune system and the tumor, identifying specific immune markers with potential diagnostic value. The article describes the complex processes involved in tumor growth, including its interaction with surrounding tissues, the development of the tumor microenvironment, and the role of stem cells. It also provides an analysis of current treatment options and the challenges they face, particularly in relation to tumor resistance. The article concludes with a thorough examination of the changing landscape of diagnostic and therapeutic approaches. It highlights notable recent research findings and provides insight into potential advancements that could shape the future of medical interventions for glioblastoma.

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M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single‐cell and bulk RNA‐Seq analysis

Cited by 3 publications

References 54 publications

MU-BRAIN: MUltiethnic Brain Rna-seq for Alzheimer INitiative

MU-BRAIN: MUltiethnic Brain Rna-seq for Alzheimer INitiative

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women

Glioblastoma: A molecular insight into current discoveries and treatment directions

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