CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

Liu, Liling; Yang, Yuan-Zhong; Duan, Hao; He, Jiahua; Sun, Lu; Hu, Wanming; Zeng, Jing

doi:10.3389/fonc.2021.611038

Cited by 23 publications

(31 citation statements)

References 47 publications

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“…CHI3L1 was found in a subset of activated astrocytes [ 16 ], monocytes/macrophages [ 12 ]. CHI3L2 has been detected in macrophages [ 17 ]; curiously, it has been reported in neuronal cells from the cerebral cortex ( ), but its expression in ALS tissues has not been described so far. As such, the origin of CSF CHI3L2 is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

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Section: Discussionmentioning

confidence: 99%

“…CHI3L1 was detected in a subset of activated astrocytes in the white matter of the motor cortex and spinal cord of ALS patients [ 16 ], as well as in monocytes/macrophages, chondrocytes, synovial cells and osteoclasts [ 12 ]. CHI3L2 has been detected in macrophages, tumor cells [ 17 ] and cartilage chondrocytes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

et al. 2021

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“…The TME includes a repertoire of cell clusters (such as tumor cells, immune cells, and fibroblasts) and plays a diverse role in cancer biology [ 49 ]. Previous research suggested that the main difficulty in treating glioma is the therapeutic resistance owing to its complex metabolic characteristics and highly immunosuppressive microenvironment [ 50 ]. However, the relationship between CISD2 and immune infiltration in glioma remains unclear.…”

Section: Discussionmentioning

confidence: 99%

High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma

et al. 2022

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Glioma is a serious disease burden globally, with high mortality and recurrence rates. CDGSH iron sulfur domain 2 (CISD2) is an evolutionarily conserved protein that is involved in several cancers. However, its role in the prognosis and immune infiltration in glioma remains unclear. In our research, RNA-seq matrix and clinicopathological relevant data for CISD2 were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Human Protein Atlas was used to verify the CISD2 protein level in glioma, and STRING was used to establish relative coexpression gene network. The Kaplan-Meier plotter was adopted to analyze the effect of CISD2 on prognosis. The connection between CISD2 expression and immune infiltration was analyzed using single-sample GSEA (ssGSEA), TIMER, and GEPIA. In contrast to normal tissues, CISD2 expression was significantly higher in glioma tissues, and CISD2 presented a certain diagnostic value in distinguishing glioma tissues from normal tissues. Furthermore, the CISD2 level was correlated with age, histologic grade, histological type, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion status, and primary therapy outcome of glioma, while high CISD2 mRNA expression was correlated with grave overall survival. Multivariate analysis demonstrated that CISD2 was an independent risk factor for patients with glioma. Functional enrichment analysis indicated that CISD2 could regulate proliferation, immune reaction, and mitochondrial function. The results from the ssGSEA and TIMER databases confirmed that CISD2 acts a prominent role in immune cell infiltration in the tumor microenvironment, especially in low-grade glioma (LGG). Furthermore, CISD2 expression was observably correlated to M2 polarization in macrophages with glioma progression. This is the first research to investigate the immune role of CISD2 in glioma. CISD2 may be an innovative prognostic biomarker and can act as a potential target for future therapy for glioma.

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“…CHI3L2 is secreted by astrocytes and is a secretory protein. It can induce an autoimmune response (Liu et al, 2021 ). Studies have shown that this gene primarily plays a role in inflammation, and its overexpression is associated with a variety of pathological conditions (Kzhyshkowska et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Microbiome, Transcriptome, and Metabolomic Analyses Revealed the Mechanism of Immune Response to Diarrhea in Rabbits Fed Antibiotic-Free Diets

et al. 2022

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In this study, diarrhea was induced in rabbits by feeding them antibiotic-free feed. The gut provides important defense against the barriers of the body, of which the duodenum is an important part to help digest food and absorb nutrients. However, the mechanisms underlying the roles of the gut microbiome and fecal metabolome in rabbit diarrhea caused by feeding an antibiotic-free diet have not been characterized. Recently, only a single study has been conducted to further characterize the antibiotic-free feed additives that caused diarrhea in weaned rabbits. The multi-omics techniques, including 16S rRNA sequencing, transcriptome sequencing, and LC-MS analysis, were combined to analyze the gut microbial compositions and functions. They also determined the fecal metabolomic profiles of diarrhea in rabbits caused by feeding antibiotic-free feed. The results showed that the liver, duodenal, and sacculus rotundus tissues of diarrhea rabbits were diseased, the composition of intestinal microbes was significantly changed, the diversity of intestinal microbes was decreased, and the distribution of intestinal microbe groups was changed. Functional analysis based on the cluster of GO and KEGG annotations suggested that two functional GO categories belonged to the metabolism cluster, and five KEGG pathways related to the metabolic pathways were significantly enriched in diarrhea rabbits. Moreover, real-time quantitative PCR (RT-qPCR) was used to verify the significant expression of genes related to diarrhea. Metabolomics profiling identified 432 significantly differently abundant metabolites in diarrhea rabbits, including amino acids and their derivatives. These amino acids were enriched in the tryptophan metabolic pathway. In addition, the functional correlation analysis showed that some altered gut microbiota families, such as Parasutterella, significantly correlated with alterations in fecal metabolites. Collectively, the results suggested that altered gut microbiota was associated with diarrhea caused by antibiotic-free feed additives in weaned rabbit pathogenesis.

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CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

Cited by 23 publications

References 47 publications

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma

Microbiome, Transcriptome, and Metabolomic Analyses Revealed the Mechanism of Immune Response to Diarrhea in Rabbits Fed Antibiotic-Free Diets

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